Abstract
The ability to simulate sedimentation velocity (SV) analytical ultracentrifugation (AUC) experiments has proved to be a valuable tool for research planning, hypothesis testing, and pedagogy. Several options for SV data simulation exist, but they often lack interactivity and require up-front calculations on the part of the user. This work introduces SViMULATE, a program designed to make AUC experimental simulation quick, straightforward, and interactive. SViMULATE takes user-provided parameters and outputs simulated AUC data in a format suitable for subsequent analyses, if desired. The user is not burdened by the necessity to calculate hydrodynamic parameters for simulated macromolecules, as the program can compute these properties on the fly. It also frees the user of decisions regarding simulation stop time. SViMULATE features a graphical view of the species that are under simulation, and there is no limit on their number. Additionally, the program emulates data from different experimental modalities and data-acquisition systems, including the realistic simulation of noise for the absorbance optical system. The executable is available for immediate download.
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Data availability
A compiled version of the software is freely available at https://www.utsouthwestern.edu/research/core-facilities/mbr/software.
References
Beazley DM (1996) Using SWIG to control, prototype, and debug C programs with Python. https://www.legacy.python.org/workshops/1996-06/papers/. Accessed 6 Feb 2023
Behlke J, Ristau O (2002) A new approximate whole boundary solution of the Lamm differential equation for the analysis of sedimentation velocity experiments. Biophys Chem 95:59–68
Brautigam CA, Deka RK, Liu WZ, Norgard MV (2018) Crystal structures of MglB-2 (TP0684), a topologically variant D-glucose-binding protein from Treponema pallidum, reveal a ligand-induced conformational change. Protein Sci 27:880–885
Brautigam CA, Tso S-C, Deka RK et al (2020) Using modern approaches to sedimentation velocity to detect conformational changes in proteins. Eur Biophys J 49:729–743
Brown PH, Schuck P (2008) A new adaptive grid-size algorithm for the simulation of sedimentation velocity profiles in analytical ultracentrifugation. Comput Phys Commun 178:105–120
Burnham B, Nass S, Kong E et al (2015) Analytical ultracentrifugation as an approach to characterize recombinant adeno-associated viral vectors. Hum Gene Ther Methods 26:228–242
Cao W, Demeler B (2008) Modeling analytical ultracentrifugation experiments with an adaptive space-time finite element solution for multicomponent reacting systems. Biophys J 95:54–65
Claverie J-M, Dreux H, Cohen R (1975) Sedimentation of generalized systems of interacting particles. I. Solution of systems of complete Lamm equations. Biopolymers 14:1685–1700
Cox DJ, Dale RS (1981) Simulation of transport experiments for interacting systems. In: Frieden C, Nichol LW (eds) Protein-protein interactions. John Wiley & Sons, New York, pp 173–211
Crank J, Nicolson P (1947) A practical method for numerical evaluation of solutions of partial differential equations of the heat-conduction type. Math Proc Cambridge Philos Soc 43:50–67
Dam J, Velikovsky CA, Mariuzza RA et al (2005) Sedimentation velocity analysis of heterogeneous protein-protein interactions: Lamm equation modeling and sedimentation coefficient distributions c(s). Biophys J 89:619–634
Fleming PJ, Fleming KG (2018) HullRad: Fast calculations of folded and disordered protein and nucleic acid hydrodynamic properties. Biophys J 114:856–869
Harris CR, Millman KJ, van der Walt SJ et al (2020) Array programming with NumPy. Nature 585:357–362
Hunter JD (2007) Matplotlib: a 2D graphics environment. Comput Sci Eng 9:90–95
Kar SR, Kingsbury JS, Lewis MS et al (2000) Analysis of transport experiments using pseudo-absorbance data. Anal Biochem 285:135–142
Kirschner MW, Schachman HK (1971a) Conformational changes in proteins as measured by difference sedimentation studies. II. Effect of stereospecific ligands on the catalytic subunit of aspartate transcarbamylase. Biochemistry 10:1919–1926
Kirschner MW, Schachman HK (1971b) Conformational changes in proteins as measured by difference sedimentation studies. I. A technique for measuring small changes in sedimentation coefficient. Biochemistry 10:1900–1919
Lamm O (1929) Die differentialgleichung der ultrazentrifugierung. Ark För Mat Astron Och Fys 21B:1–4
Ma J, Zhao H, Schuck P (2015) A histogram approach to the quality of fit in sedimentation velocity analyses. Anal Biochem 483:1–3
Maruno T, Usami K, Ishii K et al (2021) Comprehensive size distribution and composition analysis of adeno-associated virus vector by multiwavelength sedimentation velocity analytical ultracentrifugation. J Pharm Sci 110:3375–3384. https://doi.org/10.1016/j.xphs.2021.06.031
Nass SA, Mattingly MA, Woodcock DA et al (2018) Universal method for the purification of recombinant AAV vectors of differing serotypes. Mol Ther Methods Clin Dev 9:33–46
Philo JS (1996) An improved function for fitting sedimentation velocity data for low- molecular-weight solutes. Biophys J 72:435–444
Schuck P (1998) Sedimentation analysis of noninteracting and self-associating solutes using numerical solutions to the Lamm equation. Biophys J 75:1503–1512
Schuck P (2016) Sedimentation velocity analytical ultracentrifugation: discrete species and size-distributions of macromolecules and particles. CRC Press, Boca Raton
Schuck P, Demeler B (1999) Direct sedimentation analysis of interference optical data in analytical ultracentrifugation. Biophys J 76:2288–2296
Schuck P, MacPhee CE, Howlett GJ (1998) Determination of sedimentation coefficients for small peptides. Biophys J 74:466–474
Schuck P, Zhao H, Brautigam CA, Ghirlando R (2016) Basic principles of analytical ultracentrifugation. CRC Press, Boca Raton
Stafford WF (1992) Boundary analysis in sedimentation transport experiments: a procedure for obtaining sedimentation coefficient distributions using the time derivative of the concentration profile. Anal Biochem 203:295–301
Stafford WF, Sherwood PJ (2004) Analysis of heterologous interacting systems by sedimentation velocity: curve fitting algorithms for estimation of sedimentation coefficients, equilibrium and kinetic constants. Biophys Chem 108:231–243
Todd GP, Haschemeyer RH (1983) Generalized finite element solution to one-dimensional flux problems. Biophys Chem 17:321–336
Virtanen P, Gommers R, Oliphant TE et al (2020) SciPy 1.0: fundamental algorithms for scientific computing in python. Nat Methods 17:261–272
Zhao H, Ghirlando R, Piszczek G et al (2013) Recorded scan times can limit the accuracy of sedimentation coefficients in analytical ultracentrifugation. Anal Biochem 437:104–108
Acknowledgements
The author wishes to thank Dr. Peter Schuck for helpful discussions, Dr. Walter Stafford for providing exemplary code, and Drs. Lake Paul and Alexander Yarawsky for beta-testing SViMULATE and offering helpful suggestions.
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Special Issue: Analytical Ultracentrifugation 2022.
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Brautigam, C.A. SViMULATE: a computer program facilitating interactive, multi-mode simulation of analytical ultracentrifugation data. Eur Biophys J 52, 293–302 (2023). https://doi.org/10.1007/s00249-023-01637-0
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DOI: https://doi.org/10.1007/s00249-023-01637-0