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 w...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.展开更多
基金supported by the National Science Foundation of China (10732050,10872115 and 11025208)Excellent Young Scholars Research Fund of Beijing Institute of Technology
文摘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.
