医学分子生物学杂志2017，Vol.14Issue(5)：280-286,7.DOI:10.3870/j.issn.1672-8009.2017.05.000
人前列腺LRIG1蛋白三维结构同源模建及其小分子激动剂的虚拟筛选
Homology Modeling of Three-Imension Structure of Human Prostate LRIG1 Protein and Identification of Novel Hits as Its Agonist by Vir-tual Screening
摘要
Abstract
Objective LRIG1 ( tandem leucine rich-repeat sand immunoglobulin-like domains 1, LRIG1) is a newly discovered tumor suppressor gene. Recently, several studies indicated that LRIG1 expression was decreased in prostate cancer. In this study, we performed homology modeling of three-dimension structure of human prostate LRIG1 protein and structure-based virtual screening to find its functional protein, with an attempt to find a novel target for prostate cancer treat-ment. Methods By using the crystal structure ( PDB No. 3 ZYJ ) of the homologous protein (LRRC4C) of LRIG1 as a model, the 3-dimential structure of LRIG1 protein was constructed by employing MODELLER software package. In docking studies, the modeled structure was used to car-ry out the structure-based virtual screening ( SBVS ) 202490 compounds from SPEC Co. , Hol-land. The top 10 compounds ( in terms of scores awarded) were tested for molecular dynamic simula-tions of 20ns by using the AMBER and were examined for their binding mode, binding energy, hy-drogen bond interactions, the RMSD and RMSF of their molecular dynamics. Results The results showed that the synthetic 10 compounds all contained consistent binding pattern and could be used as therapeutic agents for activating LRIG1 activity. Conclusion Our screening strategy successfully found agonists with specific binding ability to human LRIG1. They might be used as chemical agents for the treatment of prostate cancer.关键词
LRIG1/前列腺肿瘤/虚拟筛选Key words
LRIG1/prostate cancer/virtual screening分类
医药卫生引用本文复制引用
张朝晖,杨安卿,黄滔,楚晨龙,赵晨晖,马斌斌,崔仁杰,周文龙..人前列腺LRIG1蛋白三维结构同源模建及其小分子激动剂的虚拟筛选[J].医学分子生物学杂志,2017,14(5):280-286,7.基金项目
上海市黄浦区科委科技项目 (No. LKW1105)This work was suppoted by a grant from the Shanghai Huangpu District Science and Technology Projects (No. LKW1105) （No. LKW1105）
