All-atom adaptively biased path optimization of Src kinase conformational inactivation: Switched electrostatic network in the concerted motion of αC helix and the activation loop.

ABSTRACT: A method to optimize a conformational pathway through a space of well-chosen reduced variables is employed to advance our understanding of protein conformational equilibrium. The adaptively biased path optimization strategy utilizes unrestricted, enhanced sampling in the region of a path in the reduced-variable space to identify a broad path between two stable end-states. Application to the inactivation transition of the Src tyrosine kinase catalytic domain reveals new insight into this well studied conformational equilibrium. The mechanistic description gained from identifying the motions and structural features along the path includes details of the switched electrostatic network found to underpin the transition. The free energy barrier along the path results from rotation of a helix, αC

SUBMITTER: Wu H 

PROVIDER: S-EPMC7789855 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature