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Essentials of Bioinformatics, Volume II pp 185–231Cite as

Molecular Modeling and Drug Design Techniques in Microbial Drug Discovery

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Abstract

Bacterial infection and its resistance have become a major human health concern worldwide, and the number of resistant bacteria is increasing daily. Hence, antibacterial agents should possess the capability of treating resistant infections and have novel mode of action. Conventional drug development approaches are time-consuming and involve huge investments, and they frequently result in failure at the clinical trial phase due side effects. Modern computational approaches are an alternative to conventional modes and are the most effective, greatly improving on the former drug target identification and optimization of the lead compound. In this chapter, we focus on the advent of a few such computational approaches and the classical methods they aid in the identification of potential lead molecules. These techniques may be used as a resource to complement drug discovery programs for novel antibiotic discovery.

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Abbreviations

AMR:

Antimicrobial resistance

BLAST:

Basic Local Alignment Search Tool

CADD:

Computer aided drug designing

CG:

Coarse-grained

CG-MD:

Coarse-grained molecular dynamics

CHARMM:

Chemistry at Harvard Macromolecular Mechanics

CoMFA:

Comparative molecular field analysis

CoMSIA:

Comparative molecular similarity indices analysis

DADA:

D-alanyl-D-alanine

DFT:

Density functional theory

DPD:

Dissipative particle dynamics

ESBLs:

Extended spectrum β-lactamases

FDA:

Food and Drug Administration

FEP:

Free-energy perturbation method

GA:

Genetic algorithms

GISA:

Glycopeptides-intermediately-resistant S. aureus

GPU:

Graphical processor unit

HTS:

High throughput screening

IUPAC:

International Union of Pure and Applied Chemistry

LB:

Ligand-based

LBDD:

Ligand-based drug design

LBVS:

Ligand-based virtual screening

MD:

Molecular dynamics

MDR:

Multi-drug resistance

MRSA:

Staphylococcus aureus resistant to methicillin

NCBI:

National Center for Biotechnology Information

NMR:

Nuclear magnetic resonance

PCA:

Principle component analysis

PCR:

Polymerase chain reaction

PK:

Pharmacokinetic

PLS:

Partial least squares

QM/MM:

Quantum mechanics/molecular mechanics

QSAR:

Quantitative structure-activity relationship

SB:

Structure-based

SBDD:

Structure-based drug design

SBVS:

Structure-based virtual screening

SI:

Sequence identity

TEIC:

Teicoplanin

VANC:

Vancomycin

References

  • Abel R, Young T, Farid R, Berne BJ, Friesner RA (2008) Role of the active-site solvent in the thermodynamics of factor Xa ligand binding. J Am Chem Soc 130:2817–2831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Abrams C, Bussi G (2014) Enhanced sampling in molecular dynamics using metadynamics, replica-exchange, and temperature-acceleration. Entropy 16:163–199

    Article  CAS  Google Scholar 

  • Accelrys Available Chemicals Directory (ACD) (2012) Accelrys, Inc., San Diego, CA

    Google Scholar 

  • Accelrys. TOPKAT (TOxicity Prediction by Komputer Assisted Technology) (2015). Available at: http://accelrys.com/products/discovery-studio/admet.html

  • Acharya C, Coop A, Polli JE, MacKerell AD (2011) Recent advances in ligand-based drug design: relevance and utility of the conformationally sampled pharmacophore approach. Curr Comput Aided Drug Des 7:10–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adcock SA, McCammon JA (2006) Molecular dynamics: survey of methods for simulating the activity of proteins. Chem Rev 106:1589–1615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Agrafiotis DK, Gibbs AC, Zhu F, Izrailev S, Martin E (2007) Conformational sampling of bioactive molecules: a comparative study. J Chem Inf Model 47:1067–1086

    Article  CAS  PubMed  Google Scholar 

  • Akamatsu M (2002) Current state and perspectives of 3D-QSAR. Curr Top Med Chem 2:1381–1394

    Article  CAS  PubMed  Google Scholar 

  • Albrich WC, Monnet DL, Harnarth S (2004) Antibiotic selection pressure and resistance in Streptococcus pneumoniae and Streptococcus pyogenes. Emerg Infect Dis 10:514–517

    Article  PubMed  PubMed Central  Google Scholar 

  • Allen TD, Eby LT, Poteet ML, Lentz E, Lima L (2004) Career benefits associated with mentoring for protégeé: a meta-analysis. J Appl Psychol 89:127–136

    Article  PubMed  Google Scholar 

  • Allen GD, Breshears DD, McDowell NG (2015) On underestimation of global vulnerability to tree mortality and forest die-off from hotter drought in the Anthropocene. Ecosphere 6:1–55

    Article  Google Scholar 

  • AltTox. Toxicity testing overview. Available at: http://alttox.org/mapp/toxicity-testing-overview/

  • An J, Totrov M, Abagyan R (2005) Pocketome via comprehensive identification and classification of ligand binding envelopes. Mol Cell Proteomics 4:752–761

    Article  CAS  PubMed  Google Scholar 

  • Anandakrishnan R, Aguilar B, Onufriev AV (2012) H++ 3.0: automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulation. Nucleic Acids Res 40:W537–41–W541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arias CA, Murray BE (2009) Antibiotic-resistant bugs in the 21 st century: a super-clinical challenge. N Engl J Med 360:439–443

    Article  CAS  PubMed  Google Scholar 

  • Ashrafuzzaman M (2014) Aptamers as both drugs and drug-carriers. Biomed Res Int 2014:697923

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Atkins P, de Paula J. (2006) Atkins’ Physical Chemistry. 8th ed. New York: Macmillan.

    Google Scholar 

  • Baker D, Sali A (2001) Protein structure prediction and structural genomics. Science 294(5540):93–96

    Article  CAS  PubMed  Google Scholar 

  • Ballester PJ, Mitchell JBO (2010) A machine learning approach to predicting protein-ligand binding affinity with applications to molecular docking. Bioinformatics (Oxford, England) 26:1169–1175

    Article  CAS  Google Scholar 

  • Barry AL, Fuchs PC, Brown SD (2001) In vitro activities of daptomycin against 2,789 clinical isolates from 11 North American medical centers. Antimicrob Agents Chemother 45:1919–1922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benigni R, Battistelli CL, Bossa C, Colafranceschi M, Tcheremenskaia O (2013) Mutagenicity, carcinogenicity, and other end points. In: Reisfeld B, Mayeno AN (eds) Computational toxicology, vol 930. Humana Press, New York, pp 67–98

    Chapter  Google Scholar 

  • Beno B, Mason J (2001) The design of combinatorail libraries using properties and 3D-pharmacophore fingerprinits. Drug Discov Today 6:251–258

    Article  CAS  PubMed  Google Scholar 

  • Berendsen HJC, Grigera JR, Straatsma TP (1987) The missing term in effective pair potentials. J Phys Chem 91(24):6269–6271

    Article  CAS  Google Scholar 

  • Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bernard D, Coop A, MacKerell AD (2005) Conformationally sampled pharmacophore for peptidic delta opioid ligands. J Med Chem 48:7773–7780

    Article  CAS  PubMed  Google Scholar 

  • Binkowski T, Naghibzadeh S, Liang J (2003) CASTp: computed atlas of surface topography of proteins. Nucleic Acids Res 31:3352–3355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blanco E, Shen H, Ferrari M (2015) Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol 33:941–951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bleicher KH, Bohm HJ, Muller K, Alanine AI (2003) Hit and lead generation: beyond high-throughput screening. Nat Rev Drug Discov 2:369–378

    Article  CAS  PubMed  Google Scholar 

  • Bolhuis PG, Chandler D, Dellago C, Geissler PL (2002) Transition path sampling: throwing ropes over rough mountain passes, in the dark. Annu Rev Phys Chem 53:291–318

    Article  CAS  PubMed  Google Scholar 

  • Borhani DW, Shaw DE (2012) The future of molecular dynamics simulations in drug discovery. J Comput Aided Mol Des 26:15–26

    Article  CAS  PubMed  Google Scholar 

  • Brady GP, Stouten PFW (2000) Fast prediction and visualization of protein binding pockets with PASS. J Comput Aided Mol Des 14:383–401

    Article  CAS  PubMed  Google Scholar 

  • Briggs JM, Marrone TJ, McCammon JA (1996) Computational science new horizons and relevance to pharmaceutical design. Trends Cardiovasc Med 6:198–206

    Article  CAS  PubMed  Google Scholar 

  • Bronzwaer SL, Bronzwaer SL, Cars O, Buchholz U, Mölstad S, Goettsch W, Veldhuijzen IK, Kool JL, Sprenger MJ, Degener JE (2002) A European study on the relationship between antimicrobial use and antimicrobial resistance. Emerg Infect Dis 8:278–282

    Article  PubMed  PubMed Central  Google Scholar 

  • Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) CHARMM – a program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem 4:187–217

    Article  CAS  Google Scholar 

  • Bryant SH, Lawrence CE (1993) An empirical energy function for threading protein sequence through the folding motif. Proteins 16(1):92–112

    Article  CAS  PubMed  Google Scholar 

  • Burger A, Abraham DJ (2006) Burger’s medicinal chemistry and drug discovery, drug discovery and drug development; Wiley, 2003. In: Langer T, Hoffmann RD (eds) Pharmacophores and Pharmacophore Searches. Wiley-VCH Verlag GmbH & Co, Weinheim

    Google Scholar 

  • Cammarata SK, Timm JA, Hempsall KA, Todd WM, Oliphant TH, Hafkin B (2000) Efficacy of linezolid in pneumonia due to penicillin intermediate and resistant Streptococcus pneumoniae. [abstract SO.OlO]. In: Programs and abstracts of the 9th International Congress on Infectious Diseases; Buenos Aires, Argentina, April 10–13. International Society of Infectious Diseases, Boston

    Google Scholar 

  • Carlson HA (2002) Protein flexibility and drug design: how to hit a moving target. Curr Opin Chem Biol 6:447–452

    Article  CAS  PubMed  Google Scholar 

  • Case DA, Cheatham TE 3rd, Darden T, Gohlke H, Luo R (2005) The Amber biomolecular simulation programs. J Comput Chem 26:1668–1688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • CASP (1999). Proteins, Structure, Function, and Genetics. CASP3 Proceeding 37:1–237

    Google Scholar 

  • Cato S (2000) Pharmacophore perception, development, and use in drug design. International University Line, La Jolla, CA, Chapter Exploring Pharmacophores with Chem-X,, pp 107–125

    Google Scholar 

  • Chang C, Swaan PW (2006) Computational approaches to modeling drug transporters. Eur J Pharm Sci 27:411–424

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Swamidass SJ, Dou Y, Bruand J, Baldi P (2005) ChemDB: a public database of small molecules and related chemoinformatics resources. Bioinformatics 21(22):4133–4139

    Article  CAS  PubMed  Google Scholar 

  • Chen JH, Linstead E, Swamidass SJ, Wang D, Baldi P (2007) ChemDB update-full-text search and virtual chemical space. Bioinformatics 23:2348–2351

    Article  CAS  PubMed  Google Scholar 

  • Chen VB, Arendall WB, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, Murray LW, Richardson SJ, Richardson DC (2010) MolProbity: allatom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr D66:12–21

    Article  CAS  Google Scholar 

  • Clark DE (2006) What has computer-aided molecular design ever done for drug discovery? Expert Opin Drug Discovery 1:103–110

    Article  CAS  Google Scholar 

  • Clark DE (2008) What has virtual screening ever done for drug discovery? Expert Opin Drug Discovery 3:841–851

    Article  CAS  Google Scholar 

  • Claussen H, Buning C, Rarey M, Lengauer T (2001) FlexE: efficient molecular docking considering protein structure variations. J Mol Biol 308:377

    Article  CAS  PubMed  Google Scholar 

  • Cohen AJ, Mori-Sánchez P, Yang W (2012) Challenges for density functional theory. Chem Rev 112:289–320

    Article  CAS  PubMed  Google Scholar 

  • Collignon P, Powers JH, Chiller TM, Aidara-Kane A, Aarestrup FM (2009) World Health Organization ranking of antimicrobials according to their importance in human medicine: a critical step for developing risk management strategies for the use of antimicrobials in food production animals. Clin Infect Dis 49:132–141

    Article  CAS  PubMed  Google Scholar 

  • Corbeil CR, Williams CI, Labute P (2012) Variability in docking success rates due to dataset preparation. J Comput Aided Mol Des 26:775–786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cornell WD, Cieplak P, Bayly CI, Gould IR, Merz KM, Ferguson DM, Spellmeyer DC, Fox T, Caldwell JW, Kollman PA (1995) A 2nd generation force-field for the simulation of proteins, nucleic acids and organic molecules. J Am Chem Soc 117:5179–5197

    Article  CAS  Google Scholar 

  • Cronin MTD (2011) In silico tools for toxicity prediction. In: Wilson AGE (ed) New horizons in predictive toxicology: current status and application. Royal Society of Chemistry, Cambridge

    Google Scholar 

  • D’Alfonso G, Tramontano A, Lahm A (2001) Structural conservation in single-domain proteins: implications for homology modeling. J Struct Biol 134:246–256

    Article  PubMed  Google Scholar 

  • Davis IW, Leaver-Fay A, Chen VB, Block JN, Kapral GJ, Wang X, Murray LW, Arendall WB, Snoeyink J, Richardson JS, Richardson DC (2007) MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res 35:W375–W383

    Article  PubMed  PubMed Central  Google Scholar 

  • Deeb O, Goodarzi M (2012) In silico quantitative structure toxicity relationship of chemical compounds: some case studies. Curr Drug Saf 7:289–297

    Article  CAS  PubMed  Google Scholar 

  • Devillers J (2013) Methods for building QSARs. In: Reisfeld B, Mayeno AN (eds) Computational toxicology, vol 930. Humana Press, New York, pp 3–27

    Chapter  Google Scholar 

  • Dias R, de Azevedo WF Jr (2008) Molecular docking algorithms. Curr Drug Targets 9(12):1040–1047

    Article  CAS  PubMed  Google Scholar 

  • DiMasi JA, Hansen RW, Grabowski HG (2003) The price of innovation: new estimates of drug developmentcosts. J Health Econ 22:151–185

    Article  PubMed  Google Scholar 

  • Dimitropoulos D, Ionides J, and Henrick K (2006) Using PDBeChem to Search the PDB Ligand Dictionary, in Current Protocols in Bioinformatics; John Wiley & Sons, 14.13.11–14.13.13.

    Google Scholar 

  • Dimitrov S, Mekenyan O (2010) An introduction to readacross for the prediction of the effects of chemicals. In: Cronin MTD, Madden JC (eds) In silico toxicology: principles and applications. The Royal Society of Chemistry, Cambridge, pp 372–384

    Chapter  Google Scholar 

  • Doernberg SB, Lodise TP, Thaden JT, Munita JM, Cosgrove SE, Arias CA, Boucher HW, Corey GR, Lowy FD, Murray B, Miller LG, Holland TL (2017) Gram-positive bacterial infections: research priorities, accomplishments, and future directions of the antibacterial resistance leadership group. Clin Infect Dis 64:S24

    Article  PubMed  PubMed Central  Google Scholar 

  • Dolinsky TJ, Czodrowski P, Li H, Nielsen JE, Jensen JH, Klebe G, Baker NA (2007) PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations. Nucleic Acids Res 35:W522–W525

    Article  PubMed  PubMed Central  Google Scholar 

  • Duncan R (2003) The dawning era of polymer therapeutics. Nat Rev Drug Discov 2:347–360

    Article  CAS  PubMed  Google Scholar 

  • Durrant J, McCammon JA (2011) Molecular dynamics simulations and drug discovery. BMC Biol 9:71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ekins S, Mestres J, Testa B (2007) In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. Br J Pharmacol 152:9–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El-Masri H (2013) Modeling for regulatory purposes (risk and safety assessment). In: Reisfeld B, Mayeno AN (eds) Computational toxicology, vol 930. Humana Press, New York, pp 297–303

    Chapter  Google Scholar 

  • Enoch SJ (2009) Chemical category formation and readacross for the prediction of toxicity. In: Puzyn T, Leszczynski J, Cronin MT (eds) Recent advances in QSAR studies, vol 8. Springer, Dordrecht, pp 209–219

    Chapter  Google Scholar 

  • Enyedy IJ, Sakamuri S, Zaman WA, Johnson KM, Wang S (2003) Pharmacophore-based discovery of substituted pyridines as novel dopamine transporter inhibitors. Bioorg Med Chem Lett 13:513–517

    Article  CAS  PubMed  Google Scholar 

  • Epik v2.2 (2011) Portland, OR: Schrödinger, Inc

    Google Scholar 

  • Ernst A, Obrecht D (2008) Case study of parallel synthesis in hit identification, hit exploration, hit-to-lead, and lead-optimization programs in high-throughput lead optimization in drug discovery. In: Kshirsagar T (ed) CRC Press, Boca Raton, USA, pp 99–116

    Google Scholar 

  • Fanelli F, Gohlke H, Kuhn LA, Morris GM, Orozco M, Pertinhez TA, Rizzi M, Sotriffer C (2008) Target flexibility: an emerging consideration in drug discovery and design. J Med Chem 51:6237–6255

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fang Y (2012) Ligand-receptor interaction platforms and their applications for drug discovery. Expert Opin Drug Discovery 7:969–988

    Article  CAS  Google Scholar 

  • Faradjian AK, Elber R (2004) Computing time scales from reaction coordinates by milestoning. J Chem Phys 120:10880–10889

    Article  CAS  PubMed  Google Scholar 

  • Faraggi E, Xue B, Zhou Y (2009) Improving the prediction accuracy of residue solvent accessibility and real-value backbone torsion angles of proteins by guided-learning through a two-layer neural network. Proteins 74:847–856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fiser A (2010) Template-based protein structure modeling. Methods Mol Biol (Clifton, NJ) 673:73–94

    Article  CAS  Google Scholar 

  • Floudas CA (2007) Computational methods in protein structure prediction. Biotechnol Bioeng 97:207–213

    Article  CAS  PubMed  Google Scholar 

  • Floudas C, Fung H, McAllister S, Moennigmann M, Rajgaria R (2006) Advances in protein structure prediction and de novo protein design: a review. Chem Eng Sci 61:966

    Article  CAS  Google Scholar 

  • Flower DR (2002) Drug design: cutting edge approaches. Royal Society of Chemistry, Cambridge

    Book  Google Scholar 

  • Frenkel D, Smit B (2001) Understanding molecular simulation. Academic Press, Inc, San Diego, p 638

    Google Scholar 

  • Frenkel D, Smit B (2002) Understanding molecular simulation: from algorithms to applications. Academic Press, San Diego

    Google Scholar 

  • Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, Repasky MP, Knoll EH, Shelley M, Perry JK, Shaw DE, Francis P, Shenkin PS (2004) Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47:1739–1749

    Article  CAS  PubMed  Google Scholar 

  • Gao JL, Truhlar DG (2002) Quantum mechanical methods for enzyme kinetics. Annu Rev Phys Chem 53:467–505

    Article  CAS  PubMed  Google Scholar 

  • Gehlhaar DK, Verkhivker GM, Rejto PA, Sherman CJ, Fogel DB, Freer ST (1995) Molecular recognition of the inhibitor AG-1343 by HIV-1 protease: conformationally flexible docking by evolutionary programming. Chem Biol 2:317–324

    Article  CAS  PubMed  Google Scholar 

  • Gehlhaar DK, Bouzida D, Rejto PA (1999) In: Parrill L, Reddy MR (eds) In rational drug design: novel methodology and practical applications, vol 719. American Chemical Society, Washington, DC, pp 292–311

    Chapter  Google Scholar 

  • Geppert H, Vogt M, Bajorath J (2010) Current trends in ligand-based virtual screening: molecular representations, data mining methods, new application areas, and performance evaluation. J Chem Inf Model 50:205–216

    Article  CAS  PubMed  Google Scholar 

  • Gilson MK, Zhou HX (2007) Calculation of protein-ligand binding affinities. Annu Rev Biophys Biomol Struct 36:21–42

    Article  CAS  PubMed  Google Scholar 

  • Giske CG, Monnet DL, Cars O, Carmeli Y (2008) Clinical and economic impact of common multidrug-resistant Gram-negative bacilli. Antimicrob Agents Chemother 52:813–821

    Article  CAS  PubMed  Google Scholar 

  • Göbl C, Madl T, Simon B, Sattler M (2014) NMR approaches for structural analysis of multidomain proteins and complexes in solution. Prog Nucl Magn Reson Spectrosc 80:26–63

    Article  PubMed  CAS  Google Scholar 

  • Gohda K, Mori I, Ohta D, Kikuchi T (2000) A CoMFA analysis with conformational propensity: an attempt to analyze the SAR of a set of molecules with different conformational flexibility using a 3D-QSAR method. J Comput Aided Mol Des 14:265–275

    Article  CAS  PubMed  Google Scholar 

  • Gohlke H, Klebe G (2001) Statistical potentials and scoring functions applied to protein-ligand binding. Curr Opin Struct Biol 11:231–235

    Article  CAS  PubMed  Google Scholar 

  • González PM, Acharya C, MacKerell AD Jr, Polli JE (2009) Inhibition requirements of the human apical sodium-dependent bile acid transporter (hASBT) using aminopiperidine conjugates of glutamyl-bile Acids. Pharm Res 26:1665–1678

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Goto E, Yagi Y, Matsumoto Y, Tsubota K (2002) Impaired functional visual acuity of dry eye patients. Am J Ophthalmol 133:181–186

    Article  PubMed  Google Scholar 

  • Guedes IA, de Magalhães CS, Dardenne LE (2014) Receptor-ligand molecular docking. Biophys Rev 6:75–87

    Article  CAS  PubMed  Google Scholar 

  • Guimaraes CRW, Cardozo M (2008) MM-GB/SA rescoring of docking poses in structure-based lead optimization. J Chem Inf Model 48:958–970

    Article  CAS  PubMed  Google Scholar 

  • Hajduk PJ, Huth JR, Fesik SW (2005) Druggability indices for protein targets derived from NMR-based screening data. J Med Chem 48:2518–2525

    Article  CAS  PubMed  Google Scholar 

  • Halgren T (2007) New method for fast and accurate binding-site identification and analysis. Chem Biol Drug Des 69:146–148

    Article  CAS  PubMed  Google Scholar 

  • Halgren TA (2009) Identifying and characterizing binding sites and assessing druggability. J Chem Inf Model 49:377–389

    Article  CAS  PubMed  Google Scholar 

  • Halgren TA, Murphy RB, Friesner RA, Beard HS, Frye LL, Pollard WT, Banks JL (2004) Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem 47:1750–1759

    Article  CAS  PubMed  Google Scholar 

  • Hamelberg D, Mongan J, McCammon JA (2004) Accelerated molecular dynamics: a promising and efficient simulation method for biomolecules. J Chem Phys 120:11919–11929

    Article  CAS  PubMed  Google Scholar 

  • Hanson SM, Newstead S, Swartz KJ, Sansom MS (2015) Capsaicin interaction with TRPV1 channels in a lipid bilayer: molecular dynamics simulation. Biophys J 108:1425–1434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harvey MJ, De Fabritiis G (2012) High-throughput molecular dynamics: the powerful new tool for drug discovery. Drug Discov Today 17:1059–1062

    Article  CAS  PubMed  Google Scholar 

  • Hawkey PM, Jones AM (2009) The changing epidemiology of resistance. J Antimicrob Chemother 64:i3–i10

    Article  CAS  PubMed  Google Scholar 

  • Hendlich M, Rippmann F, Barnickel G (1997) LIGSITE: automatic and efficient detection of potential small moleculebinding sites in proteins. J Mol Graph Model 15:359–363

    Article  CAS  PubMed  Google Scholar 

  • Herrling PL (2005) The drug discovery process. Prog Drug Res 62:1–14

    Article  CAS  PubMed  Google Scholar 

  • Hileman B (2006) Accounting for R&D, Many doubt the $800 million pharmaceutical price tag. Chemical Eng News 84:50–51

    Google Scholar 

  • Honarparvar B, Kruger HG, Maguire GE, Govender T, Soliman ME (2014) Integrated approach to structure-based enzymatic drug design: molecular modeling, spectroscopy, and experimental bioactivity. Chem Rev 114:493–537

    Article  CAS  PubMed  Google Scholar 

  • Hoofnagle AN, Resing KA, Ahn NG (2003) Protein analysis by hydrogen exchange mass spectrometry. Annu Rev Biophys Biomol Struct 32:1–25

    Article  CAS  PubMed  Google Scholar 

  • Hooft R, Vriend WG, Sander C, Abola EE (1996) Errors in protein structures. Nature 381:272

    Article  CAS  PubMed  Google Scholar 

  • Hristozov D, Oprea TI, Gasteiger J (2007) Ligand-based virtual screening by novelty detection with self-organizing maps. J Chem Inf Model 47(6):2044–2062

    Article  CAS  PubMed  Google Scholar 

  • Huang SY, Zou X (2006a) An iterative knowledge-based scoring function to predict protein-ligand interactions: I. Derivation of interaction potentials. J Comput Chem 27:1866–1875

    Article  CAS  PubMed  Google Scholar 

  • Huang SY, Zou X (2006b) An iterative knowledge-based scoring function to predict protein-ligand interactions: II. Validation of the scoring function. J Comput Chem 27:1876–1882

    Article  CAS  PubMed  Google Scholar 

  • Huang X, Lin J, Demner-Fushman D (2006) Evaluation of PICO as a knowledge representation for clinical questions. AMIA Annual Symposium proceedings. AMIA Symposium 2006:359–363

    Google Scholar 

  • Irwin JJ, Shoichet BK (2005) ZINC - a free database of commercially available compounds for virtual screening. J Chem Inf Model 45:177–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Isralewitz B, Gao M, Schulten K (2001) Steered molecular dynamics and mechanical functions of proteins. Curr Opin Struct Biol 11:224–230

    Article  CAS  PubMed  Google Scholar 

  • Jack J, Wambaugh J, Shah I (2013) Systems toxicology from genes to organs. In: Reisfeld B, Mayeno AN (eds) Computational toxicology, vol 930. Humana Press, New York, pp 375–397

    Chapter  Google Scholar 

  • Jain AN (2003) Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine. J Med Chem 46:499–511

    Article  CAS  PubMed  Google Scholar 

  • Jain AN (2006) Scoring functions for protein-ligand docking. Curr Protein Pept Sci 7:407–420

    Article  CAS  PubMed  Google Scholar 

  • Jones DT, Taylor WR, Thornton JM (1992a) The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci 3:275–282

    Google Scholar 

  • Jones DT, Taylor WR, Thornton JM (1992b) A new approach to protein fold recognition. Nature 358:86–89

    Article  CAS  PubMed  Google Scholar 

  • Jones G, Willett P, Glen RC, Leach AR, Taylor R (1997) Development and validation of a genetic algorithm for flexible docking. J Mol Biol 267:727–748

    Google Scholar 

  • Jorgensen WL, Thomas LL (2008) Perspective on free-energy perturbation calculations for chemical equilibria. J Chem Theory Comput 4:869–876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jorgensen WL, Tirado-Rives J (2005) Molecular modeling of organic and biomolecular systems using BOSS and MCPRO. J Comput Chem 26:1689–1700

    Article  CAS  PubMed  Google Scholar 

  • Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79:926–935

    Article  CAS  Google Scholar 

  • Jorgensen WL, Maxwell DS, Tirado-Rives J (1996) Development and testing of the OPLS all atom force field on conformational energetics and properties of organic liquids. J Am Chem Soc 118:11225–11236

    Article  CAS  Google Scholar 

  • Jubb H, Blundell TL, Ascher DB (2015) Flexibility and small pockets at protein–protein interfaces: new insights into druggability. Prog Biophys Mol Biol 119:2–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kahsai AW, Xiao K, Rajagopal S, Ahn S, Shukla AK, Sun J, Oas TG, Lefkowitz RJ (2011) Multiple ligand-specific conformations of the β2-adrenergic receptor. Nat Chem Biol 7:692–700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalyaanamoorthy S, Chen YP (2011) Structure-based drug design to augment hit discovery. Drug Discov Today 16:831–839

    Article  CAS  PubMed  Google Scholar 

  • Karchin R, Cline M, Mandel-Gutfreund Y, Karplus K (2003) Hidden Markov models that use predicted local structure for fold recognition: alphabets of backbone geometry. Proteins 51:504–514

    Article  CAS  PubMed  Google Scholar 

  • Karnachi P, Kulkarni A (2006) Application of pharmacophore fingerprints to structure based design and data mining. In: Langer T, Hoffmann RD (eds) Pharmacophores and pharmacophore searches. Wiley-VCH, Weinheim

    Google Scholar 

  • Karplus K, Karchin R, Draper J, Casper J, Mandel-Gutfreund Y, Diekhans M, Hughey R (2003) Combining local-structure, fold-recognition and new fold methods for protein structure prediction. Proteins 53:491–496

    Article  CAS  PubMed  Google Scholar 

  • Kaserer T, Beck KR, Akram M, Odermatt A, Schuster D (2015) Pharmacophore models and pharmacophore-based virtual screening: concepts and applications exemplified on hydroxysteroid dehydrogenases. Molecules 20:22799–22832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaveti S, Engen JR (2006) Protein interactions probed with mass spectrometry. Methods Mol Biol 316:179–197

    PubMed  Google Scholar 

  • Kelley LA, MacCallum RM, Sternberg MJ (2000) Enhanced genome annotation using structural profiles in the program 3d-pssm. J Mol Biol 299:499–520

    Article  CAS  PubMed  Google Scholar 

  • Khougaz K, Clas SD (2000) Crystallization inhibition in solid dispersions of MK-0591 and poly(vinylpyrrolidone) polymers. J Pharm Sci 89:1325–1334

    Article  CAS  PubMed  Google Scholar 

  • Kindermann C, Matthee K, Strohmeyer J, Sievert F, Breitkreutz J (2011) Tailor-made release triggering from hot-melt extruded complexes of basic polyelectrolyte and poorly watersoluble drugs. Eur J Pharm Biopharm 79:372–381

    Article  CAS  PubMed  Google Scholar 

  • King A, Phillips I (2001) The in vitro activity of daptomycin against 514 Gram-positive aerobic clinical isolates. J Antimicrob Chemother 48:219–223

    Article  CAS  PubMed  Google Scholar 

  • Kitchen DB, Decornez H, Furr JR, Bajorath J (2004) Docking and scoring in virtual screening for drug discovery:methods and application. Nat Rev Drug Discov 3:935–949

    Article  CAS  PubMed  Google Scholar 

  • Klauda JB, Venable RM, Freites JA, O’Connor JW, Tobias DJ, Mondragon-Ramirez C, Vorobyov I, MacKerell AD, Pastor RW (2010) Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J Phys Chem B 114:7830–7843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klebe G (2006) Virtual ligand screening: strategies, perspectives and limitations. Drug Discov Today 11:580–594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klebe G, Abraham U, Mietzner T (1994) Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. J Med Chem 37:4130–4146

    Article  CAS  PubMed  Google Scholar 

  • Kollman PA (1993) Free energy calculations: applications to chemical and biochemical phenomena. Chem Rev 93:2395–2417

    Article  CAS  Google Scholar 

  • Kountouris P, Hirst JD (2009) Prediction of backbone dihedral angles and protein secondary structure using support vector machines. BMC Bioinformatics 10:437

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kovalenko A (2003) Three-dimensional RISM theory for molecular liquids and solid-liquid interfaces. In: Hirata F, Mezey PG (eds) 360, vol 24. Kluwer Academic Publishers, Dordrecht, pp 169–275

    Google Scholar 

  • Kramer MS, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek JJ, Reines SA, Liu G, Snavely D, Wyatt-Knowles E, Hale JJ, Mills SG, MacCoss M, Swain CJ, Harrison T, Hill RG, Hefti F, Scolnick EM, Cascieri MA, Chicchi GG, Sadowski S, Williams AR, Hewson L, Smith D, Carlson EJ, Hargreaves RJ, Rupniak NM (1998) Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 281:1640–1645

    Article  CAS  PubMed  Google Scholar 

  • Kuntz ID, Blaney JM, Oatley SJ, Langridge R, Ferrin TE (1982) A geometric approach to macromolecule-ligand interactions. J Mol Biol 161:269–288

    Article  CAS  PubMed  Google Scholar 

  • Laio A, Parrinello M (2002) Escaping free-energy minima. Proc Natl Acad Sci U S A 99:12562–12566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Langer T, Hoffmann RD (2006) Pharmacophore modeling: application in drug discovery. Expert Opin Drug Discovery 1:261–267

    Article  CAS  Google Scholar 

  • Laskowski RA (1995 Oct) SURFNET: a program for visualizing molecular surfaces, cavities, and intermolecular interactions. J Mol Graph 13(5):323–330, 307–308

    Article  CAS  PubMed  Google Scholar 

  • Laskowski RA, Moss DS, Thornton JM (1993) Main-chain bond lengths and bond angles in protein structures. J Mol Biol 231:1049–1067

    Article  CAS  PubMed  Google Scholar 

  • Leach AR, Hann MM (2000) The in silica world of virtual libraries. Drug Discov Today 5:326–336

    Article  CAS  PubMed  Google Scholar 

  • Levitt DG, Banaszak LJ (1992 Dec) POCKET: a computer graphics method for identifying and displaying protein cavities and their surrounding amino acids. J Mol Graph 10(4):229–234

    Article  CAS  PubMed  Google Scholar 

  • Lewis K (2013) Platforms for antibiotic discovery. Nat Rev Drug Discov 12:371–387

    Article  CAS  PubMed  Google Scholar 

  • Lewis RA, Pickett SD, Clark DE (2000) Computer-aided molecular diversity analysis and combinatorial library design. Rev Comput Chem 16:1–51

    CAS  Google Scholar 

  • Lhasa Limited. Meteor Nexus (2014). Available at: http://www.lhasalimited.org

  • Li H, Robertson AD, Jensen JH (2005) Very fast empirical prediction and rationalization of protein pKa values. Proteins 61:704–721

    Article  CAS  PubMed  Google Scholar 

  • Liechty WB, Kryscio DR, Brandon VS, Peppas NA (2010) Polymers for drug delivery. Annu Rev Chem Biomol Eng 1:149–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • LigPrep v2.5 (2011) Portland, OR: Schrödinger, Inc

    Google Scholar 

  • Lin H, Truhlar DG (2007) QM/MM: what have we learned, where are we, and where do we go from here? Theor Chem Acc 117:185–199

    Article  CAS  Google Scholar 

  • Liu HY, Zou X (2006) Electrostatics of ligand binding: parametrization of the generalized born model and comparison with the Poisson-Boltzmann approach. J Phys Chem B 110:9304–9313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Livermore DM (2009) Has the era of untreatable infections arrived? J Antimicrob Chemother 64:i29–i36

    Article  CAS  PubMed  Google Scholar 

  • Lo Conte L, Brenner SE, Hubbard TJ, Chothia C, Murzin AG (2002) SCOP database in 2002: refinements accommodate structural genomics. Nucleic Acids Res 30:264–267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lonsdale R, Mulholland AJ (2014) QM/MM modelling of drugmetabolizing enzymes. Curr Top Med Chem 14:1339–1347

    Article  CAS  PubMed  Google Scholar 

  • Lyne PD, Lamb ML, Saeh JC (2006) Accurate prediction of the relative potencies of members of a series of kinase inhibitors using molecular docking and MM-GBSA scoring. J Med Chem 49:4805–4808

    Article  CAS  PubMed  Google Scholar 

  • MacKerell AD, Bashford D, Bellott M, Dunbrack RL, Evanseck JD, Field MJ (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 102:3586–3616

    Article  CAS  PubMed  Google Scholar 

  • Madan AK, Bajaj S, Dureja H (2013) Classification models for safe drug molecules. In: Reisfeld B, Mayeno AN (eds) Computational toxicology, vol 930. Humana Press, New York, pp 99–124

    Chapter  Google Scholar 

  • Mahoney MW, Jorgensen WL (2001) A five-site model for liquid water and the reproduction of the density anomaly by rigid, nonpolarizable potential functions. J Chem Phys 112:8910–8922

    Article  Google Scholar 

  • Malabarba A, Goldstein BP (2005) Origin, structure, and activity in vitro and in vivo of dalbavancin. J Antimicrob Chemother 55:15–20

    Article  CAS  Google Scholar 

  • Mandal S, Moudgil M, Mandal SK (2009) Rational drug design. Eur J Pharmacol 625:90–100

    Article  CAS  PubMed  Google Scholar 

  • Marsac PJ, Li T, Taylor LS (2009) Estimation of drugpolymer miscibility and solubility in amorphous solid dispersions using experimentally determined interaction parameters. Pharm Res 26:139–151

    Article  CAS  PubMed  Google Scholar 

  • Martin EJ, Hoeffel TJ (2000) Oriented Substituent Pharmacophore PRopErtY Space (OSPPREYS): a substituent-based calculation that describes combinatorial library products better than the corresponding product-based calculation. J Mol Graph Model 18:383–403

    Article  CAS  PubMed  Google Scholar 

  • Mason JS, Beno BR (2000) Library design using BCUT chemistry-space descriptors and multiple four-point pharmacophore fingerprints: simultaneous optimization and structure-based diversity. J Mol Graph Model 18:438–451

    Article  CAS  PubMed  Google Scholar 

  • Mason JS, Cheney DL (2000) Library design and virtual screening using multiple 4-point pharmacophore fingerprints. Pac Symp Biocomput 5:576–587

    Google Scholar 

  • McGann MR, Almond HR, Nicholls A, Grant JA, Brown FK (2003) Gaussian docking functions. Biopolymers 68:76–90

    Article  CAS  PubMed  Google Scholar 

  • Meller J, Elber R (2001) Linear programming optimization and a double statistical filter for protein threading protocols. Proteins: Struct Funct Bioinf 45:241

    Article  CAS  Google Scholar 

  • Meng X-Y, Zhang H-X, Mezei M, Cui M (2011) Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des 7(2):146–157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Menichetti F (2005) Current and emerging serious Gram-positive infections. Clin Microbiol Infect 11(s3):22–28

    Article  PubMed  Google Scholar 

  • Menikarachchi LC, Gascon JA (2010) QM/MM approaches in medicinal chemistry research. Curr Top Med Chem 10:46–54

    Article  CAS  PubMed  Google Scholar 

  • Miao X, Waddell PJ, Valafar H (2008) TALI: local alignment of protein structures using backbone torsion angles. J Bioinform Comput Biol 6:163–181

    Article  CAS  PubMed  Google Scholar 

  • Michel J, Verdonk ML, Essex JW (2006) Protein-ligand binding affinity predictions by implicit solvent simulations: a tool for lead optimization? J Med Chem 49:7427–7439

    Article  CAS  PubMed  Google Scholar 

  • Michel J, Tirado-Rives J, Jorgensen WL (2009) Prediction of the water content in protein binding sites. J Phys Chem B 113:13337–13346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Milburn D, Laskowski RA, Thornton JM (1998) Sequence annotated by structure: a tool facilitate the use of structural information in sequence analysis. Protein Eng 11:855–859

    Article  CAS  PubMed  Google Scholar 

  • Miller MS, Lay WK, Li S, Hacker WC, An J, Ren J, Elcock AH (2017) Reparameterization of protein force field nonbonded interactions guided by osmotic coefficient measurements from molecular dynamics simulations. J Chem Theory Comput 13:1812–1826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyazaki T, Aso Y, Yoshioka S, Kawanishi T (2011) Differences in crystallization rate of nitrendipine enantiomers in amorphous solid dispersions with HPMC and HPMCP. Int J Pharm 407:111–118

    Article  CAS  PubMed  Google Scholar 

  • Modi S, Hughes M, Garrow A, White A (2012) The value of in silico chemistry in the safety assessment of chemicals in the consumer goods and pharmaceutical industries. Drug Discov Today 17:134–142

    Article  CAS  Google Scholar 

  • Moellering RC, Linden PK, Reinhardt J, Blumberg EA, Bompart F (1999) The efficacy and safty of quinupristin/dalfopristin for the treatment of infection caused by vancomycin-resistant Enterococcus faecium. J Antimicrob Chemother 44:251–261

    Article  CAS  PubMed  Google Scholar 

  • Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19:1639–1662

    Article  CAS  Google Scholar 

  • Muegge I (2006) PMF scoring revisited. J Med Chem 49:5895–5902

    Article  CAS  PubMed  Google Scholar 

  • Mustata G, Follis AV, Hammoudeh DI, Metallo SJ, Wang H, Prochownik EV, Lazo JS, Bahar I (2009) Discovery of novel Myc-Max heterodimer disruptors with a three-dimensional pharmacophore model. J Med Chem 52:1247–1250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Myrianthopoulos V, Gaboriaud-Kolar N, Tallant C, Hall ML, Grigoriou S, Brownlee PM, Fedorov O, Rogers C, Heidenreich D, Wainer M, Drosos N, Mexia N, Savitsky P, Bagratuni T, Kastritis E, Terpos E, Mikros E (2016) Discovery and optimization of a selective ligand for the switch/sucrose nonfermenting-related bromodomains of polybromo protein-1 by the use of virtual screening and hydration analysis. J Med Chem 59(19):8787–8803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson DL, Lehninger AL, Cox MM (2008) Lehninger principles of biochemistry. W.H. Freeman, New York

    Google Scholar 

  • Neumann D, Lehr C-M, Lenhof H-P et al (2004) Computational modeling of the sugar-lectin interaction. Adv Drug Deliv Rev 56:437–457

    Article  CAS  PubMed  Google Scholar 

  • Nichols RL, Graham DR, Barriere SL, Rodgers A, Wilson SE, Zervos M, Dunn DL, Kreter B (1999) Treatment of hospitalized patients with complicated Gram-positive skin and skin structure infections: two randomized, multicentre studies of quinupristin/dalfopristin versus cefazolin, oxacillin or vancomycin. Synercid Skin and Skin Structure Infection Group. J Antimicrob Chemother 44:263–273

    Article  CAS  PubMed  Google Scholar 

  • Nikaido H (2003) Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 67:593–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • OECD (2015) The OECD QSAR toolbox. Available at: http://www.oecd.org/chemicalsafety/riskassessment/theoecdqsartoolbox.htm

  • Orengo CA, Bray JE, Buchan DW, Harrison A, Lee D (2002) The CATH protein family database: a resource for structural and functional annotation of genomes. Proteomics 2:11–21

    Article  CAS  PubMed  Google Scholar 

  • Österberg F, Morris GM, Sanner MF, Olson AJ, Goodsell DS (2002) Automated docking to multiple target structures: incorporation of protein mobility and structural water heterogeneity in AutoDock. Proteins 46:34–40

    Article  PubMed  CAS  Google Scholar 

  • Pallen MJ, Loman NJ, Penn CW (2010) High-throughput sequencing and clinical microbiology: progress, opportunities and challenges. Curr Opin Microbiol 13:625–631

    Article  CAS  PubMed  Google Scholar 

  • Palumbi SR (2001) Humans as the world’s greatest evolutionary force. Science 293:1786–1790

    Article  CAS  PubMed  Google Scholar 

  • Peitsch MC, Schwede T, Guex N (2000) Automated protein modelling—the proteome in 3D. Pharmacogenomics 1:257–266

    Article  CAS  PubMed  Google Scholar 

  • Pertel PE, Bernardo P, Fogarty C, Matthews P, Northland R, Benvenuto M, Thorne GM, Luperchio SA, Arbeit RD, Alder J (2008) Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia. Clin Infect Dis 46(8):1142–1151

    Article  CAS  PubMed  Google Scholar 

  • Peters JM, King RW, Höög C, Kirschner MW (1996 Nov 15) Identification of BIME as a subunit of the anaphase-promoting complex. Science 274(5290):1199–1201

    Article  CAS  PubMed  Google Scholar 

  • Peters KN, Dixon DM, Holland SM, Fauci AS (2008) The research agenda of the National Institute of Allergy and Infectious Diseases for antimicrobial resistance. J Infect Dis 197:1087–1093

    Article  PubMed  Google Scholar 

  • Petersen RK, Christensen KB, Assimopoulou AN, Fretté X, Papageorgiou VP, Kristiansen K, Kouskoumvekaki I (2011) Pharmacophore-driven identification of PPARγ agonists from natural sources. J Comput Aided Mol Des 25:107–116

    Article  CAS  PubMed  Google Scholar 

  • Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel RD, Kalé L, Schulten K (2005) Scalable molecular dynamics with NAMD. J Comput Chem 26:1781–1802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pieper U, Eswar N, Ilyin VA, Stuart A, Sali A (2002) ModBase, a database of annotated comparative protein structure models. Nucleic Acids Res 30:255–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pitt WR, Calmiano MD, Kroeplien B, Taylor RD, Turner JP, King MA (2013) Structure-based virtual screening for novel ligands. Methods Mol Biol 1008:501–519

    Article  CAS  PubMed  Google Scholar 

  • Poddar RK, Rakha P, Singh SK, Mishra DN (2010) Bioadhesive polymers as a platform for drug delivery: possibilities and future trends. Res J Pharm Dosage Forms Technol 1:40

    Google Scholar 

  • Pronk S, Pall S, Schulz R, Larsson P, Bjelkmar P (2013) GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 29:845–854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schrödinger Suite 2014-1 Protein Preparation Wizard, Epik, version 2.7; Schrödinger, LLC: New York, NY, USA, 2013

    Google Scholar 

  • Raies AB, Bajic VB (2016) In silico toxicology: computational methods for the prediction of chemical toxicity. Wiley Interdiscip Rev Comput Mol Sci 6:147–172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raizada A, Bandari A, Kumar B (2010) Polymers in drug delivery: a review. Int J Pharm Res Dev 2:9–20

    Google Scholar 

  • Rajamani R, Good AC (2007) Ranking poses in structure-based lead discovery and optimization: current trends in scoring function development. Curr Opin Drug Discov Devel 10:308–315

    CAS  PubMed  Google Scholar 

  • Ramachandran GN, Ramakrishnan C, Sasisekharan V (1963) Stereochemistry of polypeptide chain configurations. J Mol Biol 7:95–99

    Article  CAS  PubMed  Google Scholar 

  • Rarey M, Kramer B, Lengauer T, Klebe GA (1996) Fast flexible docking method using an incremental construction algorithm. J Mol Biol 261:470–489

    Article  CAS  PubMed  Google Scholar 

  • Rask-Andersen M, Almén MS, Schiöth HB (2011) Trends in the exploitation of novel drug targets. Nat Rev Drug Discov 10:579–590

    Article  CAS  PubMed  Google Scholar 

  • Reddy PD, Swarnalatha D (2010) Recent advances in novel drug delivery systems. Int J PharmTech Res 2:2025–2027

    Google Scholar 

  • Retief JD (2000) Phylogenetic analysis using PHYLIP. Methods Mol Evol 132:143–158

    Google Scholar 

  • Ripphausen P, Nisius B, Peltason L, Bajorath J (2010) Quo vadis, virtual screening? A comprehensive survey of prospective applications. J Med Chem 53:8461–8467

    Article  CAS  PubMed  Google Scholar 

  • Rocchia W, Sridharan S, Nicholls A, Alexov E, Chiabrera A, Honig B (2002) Rapid grid-based construction of the molecular surface and the use of induced surface charge to calculate reaction field energies: applications to the molecular systems and geometric objects. J Comput Chem 23:128–137

    Article  CAS  PubMed  Google Scholar 

  • Rohs R, Bloch I, Sklenar H, Shakked Z (2005) Molecular flexibility in ab-initio drug docking to DNA: binding-site and binding-mode transitions in all-atom Monte Carlo simulations. Nucleic Acids Res 33:7048–7057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rost B (2001) Review: protein secondary structure prediction continues to rise. J Struct Biol 134:204–218

    Article  CAS  PubMed  Google Scholar 

  • Rost B, Sander C (1995) Progress of 1D protein structure prediction at last. Proteins 23(3):295–300

    Article  CAS  PubMed  Google Scholar 

  • Rowe PH (2010) Statistical methods for continuous measured endpoints in in silico toxicology. In silico toxicology: Principles and applications (pp. 228–251). Cambridge, UK: The Royal Society of Chemistry

    Google Scholar 

  • Roy H, Brahma CK, Kumar R, Nandi S (2013) Formulation of saquinavir mesylate loaded microparticle by counterion induced aggregation method: approach by hyperosmotic technique. Drug Invention Today 5:259–266

    Article  CAS  Google Scholar 

  • Ruiz-Carmona S, Alvarez-Garcia D, Foloppe N (2014) rDock: a fast, versatile and open source program for docking ligands to proteins and nucleic acids. PLoS Comput Biol 10:e1003571

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rybak MJ, Hershberger E, Moldovan T, Grucz RG (2000) In vitro activities of daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin against Staphylococci and Enterococci, including vancomycinintermediate and – resistant strains. Antimicrob Agents Chemother 44:1062–1066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rychlewski L, Jaroszewski L, Li W, Godzik A (2000) Comparison of sequence profiles: strategies for structural predictions using sequence information. Protein Sci 9:232–241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salum L, Polikarpov I, Andricopulo AD (2008) Structure-based approach for the study of estrogen receptor binding affinity and subtype selectivity. J Chem Inf Model 48:2243–2253

    Article  CAS  PubMed  Google Scholar 

  • Santos Filho OA, Alencastro RB (2003) Modelagem de proteinas por homologia. Quím Nova 26:253–259

    Article  CAS  Google Scholar 

  • Sastry GM, Adzhigirey M, Day T, Annabhimoju R, Sherman W (2013) Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des 27:221–234

    Article  PubMed  CAS  Google Scholar 

  • Schäffer AA, Aravind L, Madden TL, Shavirin S, Spouge JL, Wolf YI, Koonin EV, Altschul SF (2001) Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements. Nucleic Acids Res 29:2994–3005

    Article  PubMed  PubMed Central  Google Scholar 

  • Schapira M, Abagyan R, Totrov M (2003) Nuclear hormone receptor targeted virtual screening. J Med Chem 46:3045–3059

    Article  CAS  PubMed  Google Scholar 

  • Schmaljohann D (2006) Thermo- and pH-responsive polymers in drug delivery. Adv Drug Deliv Rev 58:1655–1670

    Article  CAS  PubMed  Google Scholar 

  • Schulz-Gasch T, Stahl M (2004) Scoring functions for protein-ligand interactions: a critical perspective. Drug Discov Today Technol 1:231–239

    Article  CAS  PubMed  Google Scholar 

  • Schwartz R, Istrail S, King J (2001) Frequencies of amino acid strings in globular protein sequences indicate suppression of blocks of consecutive hydrophobic residues. Protein Sci 10:1023–1031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwede T, Kopp J, Guex N, Peitsch MC (2003) SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Res 31:3381–3385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sen S, Farooqui NA, Easwari TS, Roy B (2012) CoMFA-3D QSAR approach in drug design. Int. J. Res. Dev. Pharm. L. Sci 1:167–175

    Google Scholar 

  • Shaik S, Cohen S, Wang Y (2010) P450 enzymes: their structure, reactivity, and selectivity-modeled by QM/MM calculations. Chem Rev 110:949–1017

    Article  CAS  PubMed  Google Scholar 

  • Shan Y, Wang G, Zhou H (2001) Fold recognition and accurate query-template alignment by a combination of PSI-BLAST and threading. Proteins: Struct Funct Bioinf 42:23–37

    Article  CAS  Google Scholar 

  • Shelley JC, Cholleti A, Frye LL, Greenwood JR, Timlin MR, Uchimaya M (2007) Epik: a software program for pK (a) prediction and protonation state generation for drug-like molecules. J Comput Aided Mol Des 21:681–691

    Article  CAS  PubMed  Google Scholar 

  • Shi Y (2014) A glimpse of structural biology through X-ray crystallography. Cell 159:995–1014

    Article  CAS  PubMed  Google Scholar 

  • Shoichet BK, Stroud RM, Santi DV, Kuntz ID, Perry KM (1993) Structure-based discovery of inhibitors of thymidylate synthase. Science 259:1445–1450

    Article  CAS  PubMed  Google Scholar 

  • Silverman JA, Perlmutter NG, Shapiro HM (2003) Correlation of daptomycin bactericidal activity and membrane depolarization in Staphylococcus aureus. Antimicrob Agents Chemother 47:2538–2544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sippl MJ (1993) Recognition of errors in three-dimensional structures of proteins. Proteins 14:355–362

    Article  Google Scholar 

  • Sippl MJ, Weitckus S (1992) Detection of native‐like models for amino acid sequences of unknown three‐dimensional structure in a data base of known protein conformations. Proteins: Struct Funct Bioinf 13:258–271

    Article  CAS  Google Scholar 

  • Skolnick J, Kihara D, Zhang Y (2004) Development and large scale benchmark testing of the PROSPECTOR 3 threading algorithm. Proteins 56:502–518

    Article  CAS  PubMed  Google Scholar 

  • Sliwoski G, Kothiwale S, Meiler J, Lowe EW (2013) Computational methods in drug discovery. Pharmacol Rev 66:334–395

    Article  PubMed  CAS  Google Scholar 

  • Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE Jr (2004) Trends in antimicrobial drug development: implications for the future. Clin Infect Dis 38:1279–1286

    Article  CAS  PubMed  Google Scholar 

  • Springer J, Safley M, Huber S, Troxclair D, Craver R, Newman WP (2010) Histopathological findings in fatal novel H1N1: an autopsy case series from September-November 2009 in New Orleans. Louisiana J La State Med Soc 162:88–91

    PubMed  Google Scholar 

  • Srivastava S, Srivastava SK, Singh RB, Mishra S (2009) Computational haracterization of proteins involved in banana (Musa acuminata) ripening. Open Nutraceuticals J 2:122–126

    Article  CAS  Google Scholar 

  • Steenbergen JN, Alder J, Thorne GM, Tally FP (2005) Daptomycin: a lipopeptide antibiotic for the treatment of serious Gram-positive infections. J Antimicrob Chemother 55:283–288

    Article  CAS  PubMed  Google Scholar 

  • Sung JH, Srinivasan B, Esch MB, McLamb WT, Bernabini C, Shuler ML, Hickman JJ (2014) Using PBPK guided “Body-on-a-Chip” systems to predict mammalian response to drug and chemical exposure. Exp Biol Med 239:1225–1239

    Article  CAS  Google Scholar 

  • Talele TT, Khedkar SA, Rigby AC (2010) Successful application of computer aided drug discovery: moving drugs from concept to the clinic. Curr Top Med Chem 10:127–141

    Article  CAS  PubMed  Google Scholar 

  • Tannor DJ (2008) Introduction to quantum mechanics: a time-dependent perspective. University Science Books, Sausalito

    Google Scholar 

  • ten Brink T, Exner TE (2010) pK(a) based protonation states and microspecies for protein-ligand docking. J Comput Aided Mol Des 24:935–942

    Article  CAS  PubMed  Google Scholar 

  • Teodorescu O, Galor T, Pillardy J, Elber R (2004) Enriching the sequence substitution matrix by structural information. Proteins: Struct Funct Bioinf 54:41

    Article  CAS  Google Scholar 

  • Thomas CM, Nielsen KM (2005) Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nat Rev Microbiol 3:711–721

    Article  CAS  PubMed  Google Scholar 

  • Thompson DC, Humblet C, Joseph-McCarthy D (2008) Investigation of MM-PBSA rescoring of docking poses. J Chem Inf Model 48:1081–1091

    Article  CAS  PubMed  Google Scholar 

  • Tobi D, Elber R (2000) Distance-dependent, pair potential for protein folding: results from linear optimization. Proteins: Struct Funct Bioinf 41:40

    Article  CAS  Google Scholar 

  • Tollman PA (2001) Revolution in R&D: how genomics and genetics are transforming the biopharmaceutical industry. Boston Consulting Group, Boston

    Google Scholar 

  • Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455–461

    CAS  PubMed  PubMed Central  Google Scholar 

  • Umasankar V, Gurunathan S (2015) Drug discovery: an Appraisal. Int J Parm Pharm Sci 4:59–66

    Google Scholar 

  • Valerio LG Jr (2009) In silico toxicology for the pharmaceutical sciences. Toxicol Appl Pharmacol 241:356–370

    Article  CAS  PubMed  Google Scholar 

  • van der Kamp MW, Mulholland AJ (2013) Combined quantum mechanics/molecular mechanics (QM/MM) methods in computational enzymology. Biochemistry 52:2708–2728

    Article  PubMed  CAS  Google Scholar 

  • Van der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, HJC B (2005) GROMACS: fast, flexible, and free. J Comput Chem 26:1701–1718

    Article  CAS  Google Scholar 

  • Venkatachalam CM, Jiang X, Oldfield T, Waldman M (2003) LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites. J Mol Graph Model 21:289–307

    Article  CAS  PubMed  Google Scholar 

  • Venkatapathy R, Wang NCY (2013) Developmental toxicity prediction. In: Reisfeld B, Mayeno AN (eds) Computational toxicology, vol 930. Humana Press, New York, pp 305–340

    Chapter  Google Scholar 

  • Verma RP, Hansch C (2009) Camptothecins: a SAR/QSAR study. Chem Rev 109:213–235

    Article  CAS  PubMed  Google Scholar 

  • Vyas V, Jain A, Jain A, Gupta A (2008) Virtual screening: a fast tool for drug design. Sci Pharm 76:333–360

    Article  CAS  Google Scholar 

  • Vyas VK, Ukawala RD, Ghate M, Chintha C (2012) Homology modeling a fast tool for drug discovery: current perspectives. Indian J Pharm Sci 74(1):1–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walsh C (2003) Antibiotics: actions, origins, resistance. American Society for Microbiology (ASM) Press, Washington, DC

    Book  Google Scholar 

  • Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development and testing of a general amber force field. J Comput Chem 25:1157–1174

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Shaikh SA, Tajkhorshid E (2010) Exploring transmembrane diffusion pathways with molecular dynamics. Physiology 25:142–154

    Article  CAS  PubMed  Google Scholar 

  • WaterMap (2014) New York, NY: Schrödinger, LLC

    Google Scholar 

  • Westbrook J, Feng Z, Jain S, Bhat TN, Thanki N, Veerasamy R, Gilliland GL, Bluhm WF, Weissing H, Greer DS, Bourne PE, Berman HM (2002) The protein data bank: unifying the archive. Nucleic Acids Res 30:245–248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wheeler SR, Kearney JB, Guardiola AR, Crews ST (2006) Single-cell mapping of neural and glial gene expression in the developing Drosophila CNS midline cells. Dev Biol 294:509–524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Willett P (2006) Similarity-based virtual screening using 2D fingerprints. Drug Discov Today 11(23–24):1046–1053

    Article  CAS  PubMed  Google Scholar 

  • Wilson GL, Lill MA (2011) Integrating structure-based and ligand-based approaches for computational drug design. Future Med Chem 3:735–750

    Article  CAS  PubMed  Google Scholar 

  • Winkler DA (2002) The role of quantitative structure-activity relationships (QSAR) in biomolecular discovery. Brief Bioinform 3:73–86

    Article  CAS  PubMed  Google Scholar 

  • Wishart DS, Knox C, Guo AC, Shrivastava S, Hassanali M, Stothard P, Chang Z, Woolsey J (2006) DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res 34(Database issue):D668–D672

    Article  CAS  PubMed  Google Scholar 

  • Wolber G, Langer T (2005) LigandScout: 3-D pharmacophores derived from protein bound ligands and their use as virtual screening filters. J Chem Inf Model 45:160–169

    Article  CAS  PubMed  Google Scholar 

  • Wood MJ, Hirst JD (2005) Protein secondary structure prediction with dihedral angles. Proteins 59:476–481

    Article  CAS  PubMed  Google Scholar 

  • Woodfor N, Livermore DM (2009) Infections caused by Gram-positive bacteria: a review of the global challenge. J Infect 59:S4–S16

    Article  Google Scholar 

  • Wootton M, Howe RA, Walsh TR, Bennett PM, Macgowan AI (2000) In-vitro activity of a range of old and new antimicrobials to hetero-vancomycin-intermediate Staphylococcus aureus (hVISA) [abstract 23131. In: Program and abstract of the 40th Interscience Conference on Antimicrobial agents and chemotherapy; September 17–20, Toronto, Canada

    Google Scholar 

  • Wu S, Skolnick J, Zhang Y (2007) Ab initio modeling of small proteins by iterative TASSER simulations. BMC Biol 5:17

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xiang Z (2006) Advances in homology protein structure modeling. Curr Protein Pept Sci 7:217–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu Y, Xu D, Uberbacher EC (1998) An efficient computational method for globally optimal threading. J Comput Biol 5:597–614

    Article  CAS  PubMed  Google Scholar 

  • Yan R, Xu D, Yang J, Walker S, Zhang Y (2013) A comparative assessment and analysis of 20 representative sequence alignment methods for protein structure prediction. Sci Rep 3:2619

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang WW, Pierstorff E (2012) Reservoir-based polymer drug delivery systems. J Lab Autom 17:50–58

    Article  PubMed  CAS  Google Scholar 

  • Yang L, Wang W, Sun Q, Xu F, Niu Y, Wang C, Liang L, Xu P (2016) Development of novel proteasome inhibitors based on phthalazinone scaffold. Bioorg Med Chem Lett 26:2801–2805

    Article  CAS  PubMed  Google Scholar 

  • Yasuo K, Yamaotsu N, Gouda H, Tsujishita H, Hirono S (2009) Structure-based CoMFA as a predictive model – CYP2C9 inhibitors as a test case. J Chem Inf Model 49:853–864

    Article  CAS  PubMed  Google Scholar 

  • Yona G, Levitt M (2002) Within the twilight zone: a sensitive profile-profile comparison tool based on information theory. J Mol Biol 315:1257–1275

    Article  CAS  PubMed  Google Scholar 

  • Yoo SU, Krill SL, Wang Z, Telang C (2009) Miscibility/stability considerations in binary solid dispersion systems composed of functional excipients towards the design of multi-component amorphous systems. J Pharm Sci 98:4711–4723

    Article  CAS  PubMed  Google Scholar 

  • Young T, Abel R, Kim B, Berne BJ, Friesner RA (2007) Motifs for molecular recognition exploiting hydrophobic enclosure in protein-ligand binding. Proc Natl Acad Sci U S A 104:808–813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuriev E, Agostino M, Ramsland PA (2011) Challenges and advances in computational docking: 2009 in review. J Mol Recognit 24:149–164

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Skolnick J (2004) Automated structure prediction of weakly homologous proteins on a genomic scale. Proc Natl Acad Sci U S A 101:7594–7599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Arakaki A, Skolnick J (2005) TASSER: an automated method for the prediction of protein tertiary structures in CASP6. Proteins 61:91–98

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Liu S, Zhou Y (2008) SP5: improving protein fold recognition by using torsion angle profiles and profile-based gap penalty model. PLoS One 3:e2325

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang M, Li H, Lang B, O’Donnell K, Zhang H, Wang Z, Dong Y, Wu C, Williams RO (2012) Formulation and delivery of improved amorphous fenofibrate solid dispersions prepared by thin film freezing. Eur J Pharm Biopharm 82:534–544

    Article  CAS  PubMed  Google Scholar 

  • Zhao H, Caflisch A (2013) Discovery of ZAP70 inhibitors by high-throughput docking into a confirmation of its kinase domain generated by molecular dynamics. Bioorg Med Chem Lett 23:5721–5726

    Article  CAS  PubMed  Google Scholar 

  • Zhou H, Skolnick J (2007) Ab initio protein structure prediction using chunk-TASSER. Biophys J 93:1510–1518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou H, Zhou Y (2005) Fold recognition by combining sequence profiles derived from evolution and from depth-dependent structural alignment of fragments. Proteins 58:6321–6328

    Google Scholar 

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Authors and Affiliations

  1. School of Basic Sciences, Indian Institute of Technology, Mandi, Kamand, Himachal Pradesh, India

    Chandrabose Selvaraj

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  1. Chandrabose Selvaraj
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Editors and Affiliations

  1. Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

    Noor Ahmad Shaik

  2. Princess Dr. Najla Bint Saud Al-Saud Center for Excellence Research in Biotechnology, Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

    Khalid Rehman Hakeem

  3. Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

    Babajan Banaganapalli

  4. Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

    Ramu Elango

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Selvaraj, C. (2019). Molecular Modeling and Drug Design Techniques in Microbial Drug Discovery. In: Shaik, N., Hakeem, K., Banaganapalli, B., Elango, R. (eds) Essentials of Bioinformatics, Volume II. Springer, Cham. https://doi.org/10.1007/978-3-030-18375-2_11

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