Comparing cryo-EM methods and molecular dynamics simulation to investigate heterogeneity in ligand-bound TRPV1.

ABSTRACT: Cryogenic electron microscopy (cryo-EM) has emerged as a powerful method for resolving the structure of biological macromolecules. Recently, several computational methods have been developed to study the heterogeneity of molecules in single-particle cryo-EM. In this study, we analyze a publicly available dataset of TRPV1 using five such methods: 3DFlex, 3DVA, cryoDRGN, ManifoldEM, and Bayesian ensemble reweighting. We find significant heterogeneity, but each method produces different results, with some detecting only compositional or conformational heterogeneity. To compare these diverse results, we develop AnaVox to quantitatively determine agreement between heterogeneity methods. Furthermore, applying Bayesian ensemble reweighting combined with molecular dynamics simulations supports the

SUBMITTER: Astore MA 

PROVIDER: S-EPMC12852658 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature