Thermodynamic Characterization of Protein Folding using Monte Carlo Methods

Abstract

The study of protein folding has been a difficult challenge in molecular biology and simulation science.Recent publications showed the reproducible folding of small protein using molecular dynamics simulations. This large conformational changes can be only achieved by using specialized supercomputers [1]. In contrast to molecular dynamics simulations, Monte Carlo based simulations are not constrained solving Newton's equation of motion and therefore may be used conventional computer architectures to sample the protein folding process. Here we show fast reproducible all-atom folding transitions of the villin headpiece (Figure 1) simulated using SIMONA[2], a Monte Carlo based simulation package for nanoscale simulations including a variant of the Amber99SB∗-ILDN[3]. The results demonstrate the applicability of Monte Carlo simulation techniques to the investigation of large-scale conformational changes of proteins on conventional computer architectures. The computing time for observing folding/refolding events can be significantly reduced in comparison with molecular dynamics simulations. The thermodynamic characterization of simulated proteins can be compared with the experimental results.[1] Shaw, D. E. et al. Science 330, 341-346 (2010).[2] Wolf, M., Strunk, T. et al. J Comput Chem (2012).[3] Lindorff-Larsen et al. Science 334, 517-520 (2011).View Large Image | View Hi-Res Image | Download PowerPoint Slide