The transition between active and inactive conformations of Abl kinase studied by rock climbing and Milestoning.

ABSTRACT:

Background

Kinases are a family of enzymes that catalyze the transfer of the ɤ-phosphate group from ATP to a protein's residue. Malfunctioning kinases are involved in many health problems such as cardiovascular diseases, diabetes, and cancer. Kinases transitions between multiple conformations of inactive to active forms attracted considerable interest.

Method

A reaction coordinate is computed for the transition between the active to inactive conformation in Abl kinase with a focus on the DFG-in to DFG-out flip. The method of Rock Climbing is used to construct a path locally, which is subsequently optimized using a functional of the entire path. The discrete coordinate sets along the reaction path are used in a Milestoning calculation of the free energy landscape and the rate

SUBMITTER: Narayan B 

PROVIDER: S-EPMC7012767 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature