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

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.

Probing the mechanosensitivity in cell adhesion and migration: Experiments and modeling

Cell adhesion and migration are basic physiolog- ical processes in living organisms. Cells can actively probe their mechanical micro-environment and respond to the ex- ternal stimuli through cell adhesion. Cells need to move to the targeting place to perform function via cell migration. For adherent cells, cell migration is mediated by cell-matrix adhesion and cell-cell adhesion. Experimental approaches, especially at early stage of investigation, are indispensable to studies of cell mechanics when even qualitative behaviors of cell as well as fundamental factors in cell behaviors are unclear. Currently, there is increasingly accumulation of ex- perimental data of measurement, thus a quantitative formula- tion of cell behaviors and the relationship among these fun- damental factors are highly needed. This quantitative under- standing should be crucial to tissue engineering and biomed- ical engineering when people want to accurately regulate or control cell behaviors from single cell level to tissue level. In this review, we will elaborate recent advances in the ex- perimental and theoretical studies on cell adhesion and mi- gration, with particular focuses laid on recent advances in experimental techniques and theoretical modeling, through which challenging problems in the cell mechanics are sug- gested.