Inhibitor design for TMPRSS2: insights from computational analysis of its backbone hydrogen bonds using a simple descriptor.

ABSTRACT: Transmembrane protease serine 2 (TMPRSS2) is an important drug target due to its role in the infection mechanism of coronaviruses including SARS-CoV-2. Current understanding regarding the molecular mechanisms of known inhibitors and insights required for inhibitor design are limited. This study investigates the effect of inhibitor binding on the intramolecular backbone hydrogen bonds (BHBs) of TMPRSS2 using the concept of hydrogen bond wrapping, which is the phenomenon of stabilization of a hydrogen bond in a solvent environment as a result of being surrounded by non-polar groups. A molecular descriptor which quantifies the extent of wrapping around BHBs is introduced for this. First, virtual screening for TMPRSS2 inhibitors is performed by molecular docking using the program DOCK 6 with a

SUBMITTER: Ugrani S 

PROVIDER: S-EPMC10853362 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature