Rapid and accurate structure-based therapeutic peptide design using GPU accelerated thermodynamic integration.

ABSTRACT: Peptide-based therapeutics are an alternative to small molecule drugs as they offer superior specificity, lower toxicity, and easy synthesis. Here we present an approach that leverages the dramatic performance increase afforded by the recent arrival of GPU accelerated thermodynamic integration (TI). GPU TI facilitates very fast, highly accurate binding affinity optimization of peptides against therapeutic targets. We benchmarked TI predictions using published peptide binding optimization studies. Prediction of mutations involving charged side-chains was found to be less accurate than for non-charged, and use of a more complex 3-step TI protocol was found to boost accuracy in these cases. Using the 3-step protocol for non-charged side-chains either had no effect or was detrimental. We use t

SUBMITTER: Garton M 

PROVIDER: S-EPMC8091910 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature