Fragment Hits: What do They Look Like and How do They Bind?

ABSTRACT: A "fragment hit", a molecule of low molecular weight that has been validated to bind to a target protein, can be an effective chemical starting point for a drug discovery project. Our ability to find and progress fragment hits could potentially be improved by enhancing our understanding of their binding properties, which to date has largely been based on tacit knowledge and reports from individual projects. In the work reported here, we systematically analyzed the molecular and binding properties of fragment hits using 489 published protein-fragment complexes. We identified a number of notable features that these hits tend to have in common, including preferences in buried surface area upon binding, hydrogen bonding and other directional interactions with the protein targets, structural to

SUBMITTER: Giordanetto F 

PROVIDER: S-EPMC6466478 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature