1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
Design of Potential Aminopeptidase N (APN) inhibitors via Pharmacophore and Docking-Based Virtual Screening
Paper ID : 1252-ICB10
Authors:
Majid Pourzamani molan *
Department of Medicinal Chemistry, School of Pharmacy,Zanjan University of Medical Sciences,zanjan
Abstract:
Introduction
M1 family of metalloamineopeptidases. The enzyme aminopeptidase N regulates various of cellular Aminopeptidase N (APN), also known as CD13, is a metal-dependent membrane protease belonging to the functions by different mechanisms, such as peptide breakdown [1]. Aminopeptidase N has a significant effect on various cellular pathways, including migration, invasion, angiogenesis, and tumor cell metastasis [2]. Overexpression of APN with many diseases such as inflammation, viral infection and especially cancer. Since the enzyme aminopeptidase N plays a crucial role in cancer cell metastasis, it is now considered an attractive target for designing of anticancer drugs [3]. Drug design using computers today is dramatically increasing due to its advantages such as low cost, high speed, and good accuracy [4]. By using informatics, it is possible to identify new effective and robust compounds. In this study, a hybrid strategy including docking and virtual screening was used to identify new APN inhibitors.
Method
The crystal structure of porcine aminopeptidase-N complexed with bestatin, with the PDB ID of 4fkk, was obtained from Protein Data Bank (www.rcsb.org). A proper pharmacophore model was generated using Ligand Scout 3.12 on the most critical area on the APN active site. Then ZINC libraries (over 35 million compounds) were applied for virtual screening.
Results and Discussion
Collected compounds from virtual screening were followed by molecular docking studies. Seven compounds were selected based on docking score and complying with Lipinski’s “rule of five”. Selected compounds can be considered as a proper candidate in order to develop new APN inhibitors.
Keywords:
Virtual Screening, Molecular Docking, Aminopeptidase N, Inhibitor
Status : Paper Accepted (Poster Presentation)