The Arch from the Stones: Understanding Protein Folding Energy Landscapes via Bioinspired Collective Variables.

ABSTRACT: Protein folding remains a formidable challenge despite significant advances, particularly in sequence-to-structure prediction. Accurately capturing thermodynamics and intermediates via simulations demands overcoming time scale limitations, making effective collective variable (CV) design for enhanced sampling crucial. Here, we introduce a strategy to automatically construct complementary, bioinspired CVs. These uniquely capture local hydrogen bonding─explicitly distinguishing protein-protein from protein-water interactions─and side-chain packing, taking into account both native and non-native contacts to enhance state resolution. Using these CVs in combination with advanced enhanced sampling methods, we simulate the folding of Chignolin and TRP-cage, validating our approach against extensi

SUBMITTER: Rizzi V 

PROVIDER: S-EPMC12451740 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature