Challenges in protein-folding simulations

• Published in: Nature physics Vol. 6; no. 10; pp. 751 - 758
• Main Authors: Schulten, Klaus, Freddolino, Peter L, Harrison, Christopher B, Liu, Yanxin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2010; Nature Publishing Group
• Subjects: Amino acids; Atomic; Cellular biology; Classical and Continuum Physics; Complex Systems; Computer simulation; Condensed Matter Physics; Folding; Mathematical and Computational Physics; Molecular; Molecular dynamics; Molecular physics; Optical and Plasma Physics; Physics; Physics and Astronomy; Potential energy; Protein folding; Proteins; review-article; Sampling; Simulation; Temporal logic; Theoretical
• ISSN: 1745-2473; 1745-2481
• DOI: 10.1038/nphys1713

Experimental studies of protein folding are hampered by the fact that only low-resolution structural data can be obtained with sufficient temporal resolution. Molecular dynamics simulations offer a complementary approach, providing extremely high-resolution spatial and temporal data on folding processes. However, at present, such simulations are limited in several respects, including the inability of molecular dynamics force fields to completely reproduce the true potential energy surfaces of proteins, the need for simulations to extend to the millisecond timescale for the folding of many proteins and the difficulty inherent in obtaining sufficient sampling to properly characterize the extremely heterogeneous folding processes and then analysing those data efficiently. We review recent progress in the simulation of three common model systems for protein folding, and discuss how advances in technology and theory are allowing protein-folding simulations to address their present shortcomings. A protein’s shape is crucial for fulfilling its function within a cell. This Review discusses how molecular dynamics simulations have given us insight into the processes that turn a linear chain of amino acids into a unique three-dimensional protein.