An Empirical Biasing Force Constant to Minimize Overfitting in Cryo-EM Flexible Fitting Refinement.

ABSTRACT: Reliable modeling of protein structures from a cryo-EM density map is one of the central issues in structural biology. Typically, the constructed model is refined using a flexible fitting method combined with molecular dynamics, where a biasing potential is introduced to guide the protein structure toward the density map. However, the appropriate force constant for the biasing potential is generally unknown a priori. Here, we propose an empirical force constant that enables flexible fitting refinement with minimal overfitting. The rule is derived from systematic flexible fitting calculations performed on 29 selected systems (map resolution = 3.0-6.8 Å) using a range of force constants from weak to strong values. The refined structures are evaluated based on the MolProbity score and seconda

SUBMITTER: Matsuoka D 

PROVIDER: S-EPMC12458688 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature