Computational Simulation for Binding Interaction of TLR5 with Flagellin
TLR5 recognizes bacterial flagellin mobilizes the nuclear factor-κB (NF-κB) pathway and triggers inflammatory responses and immunoreactions.However,knowledge of the binding mechanism between TLR5 and flagellin is very limited.In this study,we apply homology modeling,protein docking,ASA and free energy calculation to probe the binding interactions between TLR5 and flagellin.First,three-dimensional structure of TLR5 was predicted using homology modeling.Then numerous predicted complexes were generated by protein docking with ZDOCK.The resulted complexes were clustered and obtained four appropriate complexes,based on experimental information.By examining the stability of the plausible candidates through unrestrained molecular dynamics (MD) simulations,calculation of free energies and ASAs,together with computational mutagenesis,a final reasonable TLR5-flagellin complex was identified.In the obtained complex model,TLR5 mainly used its concave β-sheets domains to associate the conserved α-helixes sites of flagellin.Computational mutagenesis and structure analysis characterized that the residues R90,L94,Q97 and E114 of TLR5; R392 and D393 of flagellin are most essential in the binding.These simulation results are in agreement with experimental data,which finally point out that protein docking procedures integrated with free energy simulation and computational mutagenesis are powerful tools for modeling protein complexes interactions.
TLR5 Flagellin Protein docking MD simulations Free energy
Wei Long Jinhang Zan Zewei Zhou Xin He Jin Jin Saijun Fan Peixun Liu
Institute of Radiation Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, TianjinKey Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China
国际会议
2013 International Conference on Computational Science and Engineering(2013年计算科学与工程国际学术研讨会)
青岛
英文
215-225
2013-07-01（万方平台首次上网日期，不代表论文的发表时间）