Unexpected similarity between HIV-1 reverse transcriptase and tumor necrosis factor binding sites revealed by computer vision.

ABSTRACT: Rationalizing the identification of hidden similarities across the repertoire of druggable protein cavities remains a major hurdle to a true proteome-wide structure-based discovery of novel drug candidates. We recently described a new computational approach (ProCare), inspired by numerical image processing, to identify local similarities in fragment-based subpockets. During the validation of the method, we unexpectedly identified a possible similarity in the binding pockets of two unrelated targets, human tumor necrosis factor alpha (TNF-α) and HIV-1 reverse transcriptase (HIV-1 RT). Microscale thermophoresis experiments confirmed the ProCare prediction as two of the three tested and FDA-approved HIV-1 RT inhibitors indeed bind to soluble human TNF-α trimer. Interestingly, the herein discl

SUBMITTER: Eguida M 

PROVIDER: S-EPMC8609734 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature