Identification and characterization of fragment binding sites for allosteric ligand design using the site identification by ligand competitive saturation hotspots approach (SILCS-Hotspots).

ABSTRACT:

Background

Fragment-based ligand design is used for the development of novel ligands that target macromolecules, most notably proteins. Central to its success is the identification of fragment binding sites that are spatially adjacent such that fragments occupying those sites may be linked to create drug-like ligands. Current experimental and computational approaches that address this problem typically identify only a limited number of sites as well as use a limited number of fragment types.

Methods

The site-identification by ligand competitive saturation (SILCS) approach is extended to the identification of fragment bindings sites, with the method termed SILCS-Hotspots. The approach involves precomputation of the SILCS FragMaps following which the identification of Hotspots

SUBMITTER: MacKerell AD 

PROVIDER: S-EPMC7029399 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature