Computational compensatory mutation discovery approach: Predicting a PARP1 variant rescue mutation.

ABSTRACT: The prediction of protein mutations that affect function may be exploited for multiple uses. In the context of disease variants, the prediction of compensatory mutations that reestablish functional phenotypes could aid in the development of genetic therapies. In this work, we present an integrated approach that combines coevolutionary analysis and molecular dynamics (MD) simulations to discover functional compensatory mutations. This approach is employed to investigate possible rescue mutations of a poly(ADP-ribose) polymerase 1 (PARP1) variant, PARP1 V762A, associated with lung cancer and follicular lymphoma. MD simulations show PARP1 V762A exhibits noticeable changes in structural and dynamical behavior compared with wild-type (WT) PARP1. Our integrated approach predicts A755E as a possi

SUBMITTER: Ravishankar K 

PROVIDER: S-EPMC9617126 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature