2024Dahmani MDFF

Citation

Dahmani, Zakaria L. / Scott, Ana Ligia / Vénien-Bryan, Catherine / Perahia, David / Costa, Mauricio G. S. MDFF_NM: Improved Molecular Dynamics Flexible Fitting into Cryo-EM Density Maps with a Multireplica Normal Mode-Based Search. 2024. J. Chemical Information and Modeling, Vol. 64, No. 13, p. 5151-5160

Abstract

Molecular Dynamics Flexible Fitting (MDFF) is a widely used tool to refine high-resolution structures into cryo-EM density maps. Despite many successful applications, MDFF is still limited by its high computational cost, overfitting, accuracy, and performance issues due to entrapment within wrong local minima. Modern ensemble-based MDFF tools have generated promising results in the past decade. In line with these studies, we present MDFF_NM, a stochastic hybrid flexible fitting algorithm combining Normal Mode Analysis (NMA) and simulation-based flexible fitting. Initial tests reveal that, besides accelerating the fitting process, MDFF_NM increases the diversity of fitting routes leading to the target, uncovering ensembles of conformations in closer agreement with experimental data. The potential integration of MDFF_NM with other existing methods and integrative modeling pipelines is also discussed.

Links

https://pubs.acs.org/doi/full/10.1021/acs.jcim.3c02007