Docking study for the mechanism of a novel Ras inhibitor
Focal-adhesion kinase (FAK) is a non-receptor protein tyrosine kinase which is a key regulator of survival,proliferation,migration,and invasion.It is widely accepted that FAK over-expressed and activated in various human cancers,implicating a role for FAK in carcinogenesis.In the previous work of our lab,four molecular compounds (No.95-98) which could inhibit the activity of FAK transcription were selected via luciferase assay,and the target was concentrated into Ras which played important role in signal transduction pathways via switching bind with GTP and GDP.While most inhibitors were designed based on famesyltransferase,here,we prided a serious novel lead compounds for targeting GDP pocket.In our study,we analyzed the affinity of each compound with Ras as so to predict their pharmacodynamic action via docking and identify the potential hydrogen bonds of Ras residues with discovery studio 2.5 and Autodock 4.0 (The Scripps Research Institute,La Jolla,Cal.).Glu31 and Va129 were identified as the contributor of the hydrogen bonding with No.95-98 which was first reported as Ras inhibitor via competing binding with GDP pocket.
Xinying Chen Xiao Zang Zichun Hua Jiahuang Li
State key of pharmaceutical biotechnology, School of Life Science, Nanjing University, Nanjing, China
国际会议
南京
英文
214-215
2012-05-13（万方平台首次上网日期，不代表论文的发表时间）