Evolutionary druggability: leveraging low-dimensional fitness landscapes towards new metrics for antimicrobial applications.

ABSTRACT: The term "druggability" describes the molecular properties of drugs or targets in pharmacological interventions and is commonly used in work involving drug development for clinical applications. There are no current analogues for this notion that quantify the drug-target interaction with respect to a given target variant's sensitivity across a breadth of drugs in a panel, or a given drug's range of effectiveness across alleles of a target protein. Using data from low-dimensional empirical fitness landscapes composed of 16 β-lactamase alleles and seven β-lactam drugs, we introduce two metrics that capture (i) the average susceptibility of an allelic variant of a drug target to any available drug in a given panel ("variant vulnerability"), and (ii) the average applicabil

SUBMITTER: Guerrero RF 

PROVIDER: S-EPMC10104179 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature