MutSα's Multi-Domain Allosteric Response to Three DNA Damage Types Revealed by Machine Learning.

ABSTRACT: MutSα is a key component in the mismatch repair (MMR) pathway. This protein is responsible for initiating the signaling pathways for DNA repair or cell death. Herein we investigate this heterodimer's post-recognition, post-binding response to three types of DNA damage involving cytotoxic, anti-cancer agents-carboplatin, cisplatin, and FdU. Through a combination of supervised and unsupervised machine learning techniques along with more traditional structural and kinetic analysis applied to all-atom molecular dynamics (MD) calculations, we predict that MutSα has a distinct response to each of the three damage types. Via a binary classification tree (a supervised machine learning technique), we identify key hydrogen bond motifs unique to each type of damage and suggest residues for experiment

SUBMITTER: Melvin RL 

PROVIDER: S-EPMC6959842 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature