Free energy landscapes of two model peptides: α-helical and β-hairpin peptides explored with Brownian dynamics simulation

Abstract

We applied an atomistic Brownian dynamics (BD) simulation with multiple time step method for the folding simulation of a 13-mer α-helical peptide and a 12-mer β-hairpin peptide, giving successful folding simulations. In this model, the driving energy contribution towards folding came from both electrostatic and van der Waals interactions for the α-helical peptide and from van der Waals interactions for the β-hairpin peptide. Although, many non-native structures having the same or lower energy than that of native structure were observed, the folded states formed the most populated cluster when the structures obtained by the BD simulations were subjected to the cluster analysis based on distance-based root mean square deviation of side-chains between different structures. This result indicates that we can predict the native structures from conformations sampled by BD simulation.

Keywords:

• Protein folding
• Brownian dynamics
• Free energy landscape
• Cluster analysis
• Structure prediction

Acknowledgements

T. Ando acknowledges support from the Academic Frontier Project from MEXT (Ministry of Education, Culture, Sports, Science and Technology of Japan). This work was supported by a Grant-in-Aid for Scientific Research on Priority Area (C) Genome Information Science from MEXT and by the Open Research Center Project from MEXT to I. Yamato.