A unique ligand-steered strategy for CC chemokine receptor 2 homology modeling to facilitate structure-based virtual screening.

ABSTRACT: CC chemokine receptor 2 (CCR2) antagonists that disrupt CCR2/MCP-1 interaction are expected to treat a variety of inflammatory and autoimmune diseases. The lack of CCR2 crystal structure limits the application of structure-based drug design (SBDD) to this target. Although a few three-dimensional theoretical models have been reported, their accuracy remains to be improved in terms of templates and modeling approaches. In this study, we developed a unique ligand-steered strategy for CCR2 homology modeling. It starts with an initial model based on the X-ray structure of the closest homolog so far, that is, CXCR4. Then, it uses Elastic Network Normal Mode Analysis (EN-NMA) and flexible docking (FD) by AutoDock Vina software to generate ligand-induced fit models. It selects optimal model(s) as

SUBMITTER: Jin H 

PROVIDER: S-EPMC8048943 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature