Interaction mode based on molecular docking and molecular dynamics simulations between ASK1 receptor and tumor suppressor RITA
We performed molecular docking and molecular dynamics (MD) simulation method to investigate the interaction between ASK1 receptors and small molecules RITA.First, the molecular docking program was used to perform the docking RITA and all active sits of ASK1,mainly related structures named as 4BF2.MD method as implemented in the DS program was used to model the best two active pockets of 4BF2 receptors and RITA compounds in water solvation environment with CHARMm force field and to optimize the docking complex structure.Based on MM-PBSA methods and Trajectory analyze programs , the dynamics trajectory monitoring of RMDS, Potential energy, Interaction Energy, VDW Interaction Energy, Electrostatic Interaction Energy were compiled.The results indicated that the active docking sites 1 and sites 3 of 4BF2-RITA complexes had better binding affinity.Hydrogen bonds and Pication bonds were formed between amino acid residues of ASK1 and RITA in both sites.the MD simulation showed good qualities judging by RMSD values within 1.5A, especially the RMSD value of 4BF2-RITA site3 complexes lower 1.0(A).Comparison the results of Potential energy, Interaction Energy, VDW Interaction Energy, Electrostatic Interaction Energy values versus time, they revealed that the site 3 of ASK1 was a active pocket, could form ASK1-RITA complex stable, which had a better kinetics balance, lower Potential energy and higher binding flexibility.Theoretically, RITA as a potential tumor suppressor is a endogenous stimulus similar in vivo ,which interact easier with the backbone of 805-882 peptides of ASK1.The binding leads to ASK1 receptor molecular conformational change to an activate conformation.Physiologic effects may thus be triggered by a mediating signal transduction and affect its pro-apoptotic function by the activation of the ASK1 protein.
molecular dynamics ASK1 RITA molecular docking
Wu Qinghua Jiang Quan Qian Sinong Hu Jing Xiao Weiwei Zhang Bao Song Peixin Feng Xiaoli
Biosafety Level-3 (BSL-3) Laboratory, School of public health and tropical medicine, Southern Medical University, Guangdong,China
国内会议
苏州
英文
248-249
2014-10-26（万方平台首次上网日期，不代表论文的发表时间）