On the role of native contact cooperativity in protein folding

• 成果类型: Article
• 署名作者: Wang, David; Frechette, Layne B.; Best, Robert B.
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Johns Hopkins University; Brandeis University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13476
• DOI: 10.1073/pnas.2319249121
• 发表日期: 2024-05-28
• 关键词: hydrophobic interactions; nonnative interactions; hydrogen-exchange; energy landscape; phase-separation; mean force; MODEL; principles; DYNAMICS; bottlenecks

摘要

The consistency of energy landscape theory predictions with available experimental data, as well as direct evidence from molecular simulations, have shown that protein folding mechanisms are largely determined by the contacts present in the native structure. As expected, native contacts are generally energetically favorable. However, there are usually at least as many energetically favorable nonnative pairs owing to the greater number of possible nonnative interactions. This apparent frustration must therefore be reduced by the greater cooperativity of native interactions. In this work, we analyze the statistics of contacts in the unbiased all -atom folding trajectories obtained by Shaw and coworkers, focusing on the unfolded state. By computing mutual cooperativities between contacts formed in the unfolded state, we show that native contacts form the most cooperative pairs, while cooperativities among nonnative or between native and nonnative contacts are typically much less favorable or even anticooperative. Furthermore, we show that the largest network of cooperative interactions observed in the unfolded state consists mainly of native contacts, suggesting that this set of mutually reinforcing interactions has evolved to stabilize the native state.