A systematic pipeline of protein structure selection for computer-aided drug discovery: A case study on T790M/L858R mutant EGFR structures.

ABSTRACT: Virtual screening (VS) is a routine method to evaluate chemical libraries for lead identification. Therefore, the selection of appropriate protein structures for VS is an essential prerequisite to identify true actives during docking. But the presence of several crystal structures of the same protein makes it difficult to select one or few structures rationally for screening. Therefore, a computational prioritization protocol has been developed for shortlisting crystal structures that identify true active molecules with better efficiency. As identification of small-molecule inhibitors is an important clinical requirement for the T790M/L858R (TMLR) EGFR mutant, it has been selected as a case study. The approach involves cross-docking of 21 co-crystal ligands with all the structures of the s

SUBMITTER: Das AP 

PROVIDER: S-EPMC10443354 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature