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

• Published in: 力学学报：英文版 2012, Vol.28 (3), p.891-903
• Main Author: De-Chang Li Bao-Hua Ji
• Format: Article
• Language: English
• Subjects: HIV-1蛋白酶; 人类免疫缺陷病毒; 分子间; 标识; 生物分子相互作用; 自由能; 蛋白酶抑制剂; 计算精度
• ISSN: 0567-7718; 1614-3116

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.