A protein may exist as an ensem-ble of di erent conformations in solution,which cannot be repre-sented by a single static structure.Molecular dy-namics(MD)simulation has become a useful tool for sampling protein confo...A protein may exist as an ensem-ble of di erent conformations in solution,which cannot be repre-sented by a single static structure.Molecular dy-namics(MD)simulation has become a useful tool for sampling protein conformations in solution,but force elds and water models are important issues.This work presents a case study of the bacteriophage T4 lysozyme(T4L).We have found that MD simulations using a classic AMBER99SB force eld and TIP4P water model cannot well describe hinge-bending domain motion of the wild-type T4L at the timescale of one microsecond.Other combinations,such as a residue-speci c force eld called RSFF2+and a dispersion-corrected water model TIP4P-D,are able to sample reasonable solution conformations of T4L,which are in good agreement with experimental data.This primary study may provide candidates of force elds and water models for further investigating conformational transition of T4L.展开更多
Binding and releasing ligands are critical for the biological functions of many proteins,so it is important to determine these highly dynamic processes.Although there are experimental techniques to determine the struc...Binding and releasing ligands are critical for the biological functions of many proteins,so it is important to determine these highly dynamic processes.Although there are experimental techniques to determine the structure of a protein-ligand complex,it only provides a static picture of the system.With the rapid increase of computing power and improved algorithms,molecular dynamics(MD)simulations have diverse of superiority in probing the binding and release process.However,it remains a great challenge to overcome the time and length scales when the system becomes large.This work presents an enhanced sampling tool for ligand binding and release,which is based on iterative multiple independent MD simulations guided by contacts formed between the ligand and the protein.From the simulation results on adenylate kinase,we observe the process of ligand binding and release while the conventional MD simulations at the same time scale cannot.展开更多
基金This work was supported by the National Natu-ral Science Foundation of China(No.91953101 and No.21573205)the Strategic Priority Research Program of the Chinese Academy of Science(XDB37040202),the Hefei National Science Center Pilot Project Funds,and the New Concept Medical Research Fund of USTC.
文摘A protein may exist as an ensem-ble of di erent conformations in solution,which cannot be repre-sented by a single static structure.Molecular dy-namics(MD)simulation has become a useful tool for sampling protein conformations in solution,but force elds and water models are important issues.This work presents a case study of the bacteriophage T4 lysozyme(T4L).We have found that MD simulations using a classic AMBER99SB force eld and TIP4P water model cannot well describe hinge-bending domain motion of the wild-type T4L at the timescale of one microsecond.Other combinations,such as a residue-speci c force eld called RSFF2+and a dispersion-corrected water model TIP4P-D,are able to sample reasonable solution conformations of T4L,which are in good agreement with experimental data.This primary study may provide candidates of force elds and water models for further investigating conformational transition of T4L.
基金supported by the National Natural Science Foundation of China(No.91953101)the Strategic Priority Research Program of the Chinese Academy of Science(XDB37040202)the Hefei National Science Center Pilot Project Funds,and the New Concept Medical Research Fund of USTC。
文摘Binding and releasing ligands are critical for the biological functions of many proteins,so it is important to determine these highly dynamic processes.Although there are experimental techniques to determine the structure of a protein-ligand complex,it only provides a static picture of the system.With the rapid increase of computing power and improved algorithms,molecular dynamics(MD)simulations have diverse of superiority in probing the binding and release process.However,it remains a great challenge to overcome the time and length scales when the system becomes large.This work presents an enhanced sampling tool for ligand binding and release,which is based on iterative multiple independent MD simulations guided by contacts formed between the ligand and the protein.From the simulation results on adenylate kinase,we observe the process of ligand binding and release while the conventional MD simulations at the same time scale cannot.
