Free energy calculation of single molecular interaction using Jarzynski's identity method:the case of HIV-1 protease inhibitor system

作     者：De-Chang Li Bao-Hua Ji 

作者机构：Biomechanics and Biomaterials LabDepartment of Applied MechanicsBeijing Institute of TechnologyKey Laboratory.of Dynamics and Control of Flight VehicleMinistry of Education100081 BeijingChina 

出 版 物：《Acta Mechanica Sinica》 (力学学报（英文版）)

年 卷 期：2012年第28卷第3期

页      面：891-903页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 070304[理学-物理化学(含∶化学物理)] 08[工学] 0817[工学-化学工程与技术] 080401[工学-精密仪器及机械] 0804[工学-仪器科学与技术] 0802[工学-机械工程] 0703[理学-化学] 0701[理学-数学] 081102[工学-检测技术与自动化装置] 0811[工学-控制科学与工程] 0801[工学-力学（可授工学、理学学位）] 0702[理学-物理学] 

基　　金：supported by the National Science Foundation of China (10732050,10872115 and 11025208) Excellent Young Scholars Research Fund of Beijing Institute of Technology 

主　　题：Molecular dynamics simulation. Single molecu lar interaction ~ Molecular biomechanics ~ Steered moleculardynamics ~ Free energy calculation 

摘      要：Jarzynski＇ identity （JI） method was suggested a promising tool for reconstructing free energy landscape of biomolecular interactions in numerical simulations and ex- periments. However, JI method has not yet been well tested in complex systems such as ligand-receptor molecular pairs. In this paper, we applied a huge number of steered molec- ular dynamics （SMD） simulations to dissociate the protease of human immunodeficiency type I virus （HIV-1 protease） and its inhibitors. We showed that because of intrinsic com- plexity of the ligand-receptor system, the energy barrier pre- dicted by JI method at high pulling rates is much higher than experimental results. However, with a slower pulling rate and fewer switch times of simulations, the predictions of JI method can approach to the experiments. These results sug- gested that the JI method is more appropriate for reconstruct- ing free energy landscape using the data taken from experi- ments, since the pulling rates used in experiments are often much slower than those in SMD simulations. Furthermore, we showed that a higher loading stiffness can produce higher precision of calculation of energy landscape because it yields a lower mean value and narrower bandwidth of work distri- bution in SMD simulations.