Metadynamics-Based Approaches for Modeling the Hypoxia-Inducible Factor 2α Ligand Binding Process.

ABSTRACT: Several methods based on enhanced-sampling molecular dynamics have been proposed for studying ligand binding processes. Here, we developed a protocol that combines the advantages of steered molecular dynamics (SMD) and metadynamics. While SMD is proposed for investigating possible unbinding pathways of the ligand and identifying the preferred one, metadynamics, with the path collective variable (PCV) formalism, is suggested to explore the binding processes along the pathway defined on the basis of SMD, by using only two CVs. We applied our approach to the study of binding of two known ligands to the hypoxia-inducible factor 2α, where the buried binding cavity makes simulation of the process a challenging task. Our approach allowed identification of the preferred entrance pathway for each l

SUBMITTER: Callea L 

PROVIDER: S-EPMC8280741 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature