How Well Do Molecular Dynamics Force Fields Model Peptides? A Systematic Benchmark Across Diverse Folding Behaviors.

ABSTRACT: Linear peptides play essential roles in biology and drug discovery, frequently mediating protein-protein interactions through short, flexible motifs. However, their structural plasticity-ranging from disordered to context-dependent folding-makes them challenging targets for molecular simulations. In this work, we benchmark the performance of twelve popular and emerging fixed-charge force fields across a curated set of twelve peptides spanning structured miniproteins, context-sensitive epitopes, and disordered sequences. Each peptide was simulated from both folded (200 ns) and extended (10 μs) states to assess stability, folding behavior, and force field biases. Our analysis reveals consistent trends: some force fields exhibit strong structural bias, others allow reversible fluctuati

SUBMITTER: Singh B 

PROVIDER: S-EPMC12324505 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature