From helix–coil transitions to protein folding

✍ Scribed by Harold A. Scheraga

• Publisher: Wiley (John Wiley & Sons)
• Year: 2008
• Tongue: English
• Weight: 111 KB
• Volume: 89
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.20890

✦ Synopsis

Abstract

An evolution of procedures to simulate protein structure and folding pathways is described. From an initial focus on the helix–coil transition and on hydrogen‐bonding and hydrophobic interactions, our original attempts to determine protein structure and folding pathways were based on an experimental approach. Experiments on the oxidative folding of reduced bovine pancreatic ribonuclease A (RNase A) led to a mechanism by which the molecule folded to the native structure by a minimum of four different pathways. The experiments with RNase A were followed by development of a molecular mechanics approach, first, making use of global optimization procedures and then with molecular dynamics (MD), evolving from an all‐atom to a united‐residue model. This hierarchical MD approach facilitated probing of the folding trajectory to longer time scales than with all‐atom MD, and hence led to the determination of complete folding trajectories, thus far for a protein containing as many as 75 amino acid residues. With increasing refinement of the computational procedures, the computed results are coming closer to experimental observations, providing an understanding as to how physics directs the folding process. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 479–485, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [email protected]