Identification of potent CypD inhibitors via pharmacophore based virtual screening, docking and molecular dynamics simulation

Cyclophilin D (CypD) is a mitochondrial matrix peptidyl prolidase that has been identified as a target for the treatment of acute pancreatitis. However, only a few compounds have been reported as CypD inhibitors. To discover novel CypD inhibitors, a ZINC database including 206,724 compounds was screened through 3D-QSAR pharmacophore model and molecular docking in sequence. After an in-depth analysis of the docking results obtained, ZINC161011368, ZINC664707610 and ZINC665010466 were selected for the molecular dynamics simulations and the binding free energy calculations. On this basis, ZINC161011368 was identified as having the potential of application as a novel CypD inhibitor. This study provides a basis for screening highly active CypD inhibitors for the treatment of acute pancreatitis. (c) 2021 Elsevier B.V. All rights reserved.