Ultra-High-Throughput Structure-Based Virtual Screening for Small-Molecule Inhibitors of Protein-Protein Interactions.

ABSTRACT: Protein-protein interactions play important roles in virtually all cellular processes, making them enticing targets for modulation by small-molecule therapeutics: specific examples have been well validated in diseases ranging from cancer and autoimmune disorders, to bacterial and viral infections. Despite several notable successes, however, overall these remain a very challenging target class. Protein interaction sites are especially challenging for computational approaches, because the target protein surface often undergoes a conformational change to enable ligand binding: this confounds traditional approaches for virtual screening. Through previous studies, we demonstrated that biased "pocket optimization" simulations could be used to build collections of low-energy pocket-containing con

SUBMITTER: Johnson DK 

PROVIDER: S-EPMC4765363 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature