Activation of Abl1 Kinase Explored Using Well-Tempered Metadynamics Simulations on an Essential Dynamics Sampled Path.

ABSTRACT: Well-tempered metadynamics (wT-metaD) simulations using path collective variables (CVs) have been successfully applied in recent years to explore conformational transitions in protein kinases and other biomolecular systems. While this methodology has the advantage of describing the transitions with a limited number of predefined path CVs, it requires as an input a reference path connecting the initial and target states of the system. It is desirable to automate the path generation using approaches that do not rely on the choice of geometric CVs to describe the transition of interest. To this end, we developed an approach that couples essential dynamics sampling with wT-metaD simulations. We used this newly developed procedure to explore the activation mechanism of Abl1 kinase and compute t

SUBMITTER: Oruganti B 

PROVIDER: S-EPMC8582261 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature