Binding Networks Identify Targetable Protein Pockets for Mechanism-Based Drug Design.

ABSTRACT: The human genome codes only a few thousand druggable proteins, mainly receptors and enzymes. While this pool of available drug targets is limited, there is an untapped potential for discovering new drug-binding mechanisms and modes. For example, enzymes with long binding cavities offer numerous prerequisite binding sites that may be visited by an inhibitor during migration from a bulk solution to the destination site. Drug design can use these prerequisite sites as new structural targets. However, identifying these ephemeral sites is challenging. Here, we introduce a new method called NetBinder for the systematic identification and classification of prerequisite binding sites at atomic resolution. NetBinder is based on atomistic simulations of the full inhibitor binding process and provide

SUBMITTER: Balint M 

PROVIDER: S-EPMC9267029 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature