Integrating Experimental and In Silico HTS in the Discovery of Inhibitors of Protein-Nucleic Acid Interactions.

ABSTRACT: Discovery of novel tool compounds and drug leads against a range of unorthodox protein targets has pushed both experimental screening methodologies as well as the field of structure-based design to the limit in recent years. Increasingly, it has been recognized that some of the most desirable targets for the development of small-molecule effectors are actually protein-protein and protein-nucleic acid interactions. There are numerous nontrivial challenges to pursuing small-molecule lead compounds directed toward PPIs and PNIs: relatively shallow cavities, large surface areas that are natively complexed to macromolecules, complex patterns of interstitial waters, a paucity of "hot spots," large conformational changes upon ligand binding, etc. Although there have been some notable successes ta

SUBMITTER: Li Q 

PROVIDER: S-EPMC6010167 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature