Excess positional mutual information predicts both local and allosteric mutations affecting beta lactamase drug resistance.

ABSTRACT:

Motivation

Bacterial resistance to antibiotics, particularly plasmid-encoded resistance to beta lactam drugs, poses an increasing threat to human health. Point mutations to beta-lactamase enzymes can greatly alter the level of resistance conferred, but predicting the effects of such mutations has been challenging due to the large combinatorial space involved and the subtle relationships of distant residues to catalytic function. Therefore we desire an information-theoretic metric to sensitively and robustly detect both local and distant residues that affect substrate conformation and catalytic activity.

Results

Here, we report the use of positional mutual information in multiple microsecond-length molecular dynamics (MD) simulations to predict residues linked to catalytic ac

SUBMITTER: Cortina GA 

PROVIDER: S-EPMC6078173 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature