ABSTRACT
An exhaustive comparison of different proteins has provided new insights into the characteristics of many proteins, leading to understanding their molecular and biological functions. Although many research works have so far characterized binding sites (BS) in proteins, only a few research-works about promiscuous BS which can accommodate different ligands or compounds have been presented and the knowledge is still limited. Thus, in this study, the promiscuous BS in protein-small molecule complexes from the Protein Data Bank (PDB) were exhaustively compared with the non-promiscuous BS to reveal physicochemical and structural properties of their BS. As a result, aliphatic, aromatic, and sulfur-containing amino acids (AA) were more likely to appear in promiscuous BS, indicating that they tend to be more hydrophobic than non-promiscuous BS. Furthermore, the number of AA and the accessible surface area of promiscuous BS tended to be larger than those of non-promiscuous BS. In addition, the significant difference of ą-helix between promiscuous BS and non-promiscuous BS was observed.
- Berman, H., Henrick, K. and Nakamura, H. "Announcing the worldwide Protein Data Bank." Nat Struct Biol, 10, 12 (Dec 2003), 980.Google Scholar
- Gao, M. and Skolnick, J. "A comprehensive survey of small-molecule binding pockets in proteins." PLoS Comput Biol, 9, 10 (Oct 2013), e1003302.Google ScholarCross Ref
- Cerisier, N., Petitjean, M., Regad, L., Bayard, Q., Reau, M., Badel, A. and Camproux, A. C. "High Impact: The Role of Promiscuous Binding Sites in Poly pharmacology." Molecules, 24, 14 (Jul 10 2019).Google ScholarCross Ref
- Li, W. and Godzik, A. "Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences." Bioinformatics, 22, 13 (Jul 1 2006), 1658--1659.Google ScholarDigital Library
- Fu, L., Niu, B., Zhu, Z., Wu, S. and Li, W. "CD-HIT: accelerated for clustering the next-generation sequencing data." Bioinformatics, 28, 23 (Dec 1 2012), 3150--3152.Google ScholarDigital Library
- Larkin, M. A., Blackshields, G., Brown, N. P., Chenna, R., McGettigan, P. A., McWilliam, H., Valentin, F., Wallace, I. M., Wilm, A., Lopez, R., Thompson, J. D., Gibson, T. J. and Higgins, D. G." Clustal W and Clustal X version 2.0. " Bioinformatics, 23, 21 (Nov 1 2007), 2947--2948.Google ScholarDigital Library
- Kawabata, T. "Build-up algorithm for atomic correspondence between chemical structures. " J Chem Inf Model, 51, 8 (Aug 22 2011), 1775--1787.Google ScholarCross Ref
- Kawabata, T. and Nakamura, H. "3D flexible alignment using 2D maximum common substructure: dependence of prediction accuracy on target-reference chemical similarity. "J Chem Inf Model, 54, 7 (Jul 28 2014), 1850--1863.Google ScholarCross Ref
- Juretic, D., Lucic, B., Zucic, D. and Trinajstic, N. "Protein transmembrane structure: recognition and prediction by using hydrophobicity scales through preference functions." Theoretical and Computational Chemistry, 5 (1998), 405--445.Google ScholarCross Ref
- Kabsch, W. and Sander, C. "Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features." Biopolymers, 22, 12 (Dec 1983), 2577--2637.Google ScholarCross Ref
Index Terms
- Study of Characterization of Promiscuous Binding Sites in Protein-Small Molecule Complexes
Recommendations
Predicting small ligand binding sites in proteins using backbone structure
Motivation: Specific non-covalent binding of metal ions and ligands, such as nucleotides and cofactors, is essential for the function of many proteins. Computational methods are useful for predicting the location of such binding sites when ...
Small molecule ligand docking to genotype specific bundle structures of hepatitis C virus (HCV) p7 protein
Display Omitted Binding poses of antivirals to hexameric bundles of p7 of HCV genotype 5a and 1b.LeadIT suggests guanidinium compounds then imino sugars, adamantanes.Rescoring with HYDE reverses the order.Favored binding sites within the pore and at ...
Comments