DIRseq as a method for predicting drug-interacting residues of intrinsically disordered proteins from sequences.

ABSTRACT: Intrinsically disordered proteins (IDPs) are now well-recognized as drug targets. Identifying drug-interacting residues is valuable for both optimizing compounds and elucidating the mechanism of action. Currently, NMR chemical shift perturbation and all-atom molecular dynamics (MD) simulations are the primary tools for this purpose. Here, we present DIRseq, a fast method for predicting drug-interacting residues from the amino-acid sequence. All residues contribute to the propensity of a particular residue to be drug-interacting; the contributing factor of each residue has an amplitude that is determined by its amino-acid type and attenuates with increasing sequence distance from the particular residue. DIRseq predictions match well with drug-interacting residues identified by NMR chemical

SUBMITTER: MacAinsh M 

PROVIDER: S-EPMC12503486 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature