Toward Developing Intuitive Rules for Protein Variant Effect Prediction Using Deep Mutational Scanning Data.

ABSTRACT: Protein structure and function can be severely altered by even a single amino acid mutation. Predictions of mutational effects using extensive artificial intelligence (AI)-based models, although accurate, remain as enigmatic as the experimental observations in terms of improving intuitions about the contributions of various factors. Inspired by Lipinski's rules for drug-likeness, we devise simple thresholding criteria on five different descriptors such as conservation, which have so far been limited to qualitative interpretations such as high conservation implies high mutational effect. We analyze systematic deep mutational scanning data of all possible single amino acid substitutions on seven proteins (25153 mutations) to first define these thresholds and then to evaluate the scope and li

SUBMITTER: Sruthi CK 

PROVIDER: S-EPMC7689672 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature