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.

Nonequilibrium Solvent Free Energy Curve from Molecular Theory in Electron Transfer Reaction

The microscopic moleeular theory for electron transfer in a model solvent ishahr developed. The nonlinear response of the solvent molecules is be computedquanitatively in a new way. Adopting computer simulation daa and choosingappropriate reaction coordinae, a reasonable free energy dinram is constructed and thercorganhaion energy for the product state is calculated.

Modeling and Simulation of Lithium Vacuum Evaporation Process Using COMSOL Multiphysics

Based on the COMSOL Multiphysics simulation software,this study carried out modeling and numerical simulation for the evaporation process of liquid metal lithium in the vacuum free molecular flow state.The motion of lithium atoms in the evaporation process was analyzed through a succession of studies.Based on the available experimental values of the saturated vapor pressure of liquid metal lithium,the relationship between saturated vapor pressure and temperature of liquid lithium in the range of 600 K-900 K was obtained.A two-dimensional symmetric model(3.5 mm×20 mm) was established to simulate the transient evaporation process of liquid lithium at wall temperatures of 750 K,780 K,800 K,810 K,825 K,and 850 K,respectively.The effects of temperature,the evaporation coefficient,back pressure,and length-to-diameter ratio on the evaporation process were studied;the variation trends and reasons of the molecular flux and the pressure during the evaporation process were analyzed.At the same time,the evaporation process under variable wall temperature conditions was simulated.This research made the evaporation process of liquid lithium in vacuum molecular flow clearer,and provided theoretical support for the space reactor and nuclear fusion related fields.

Identifying potential compounds from Bacopa monnieri(brahmi)against coxsackievirus A16 RdRp targeting HFM disease(tomato flu)

Hand,foot,and mouth disease(HFMD),primarily instigated by Coxsackievirus A16(CVA16),poses a serious health concern,necessitating effective therapeutic interventions.The RNA-dependent RNA polymerase(RdRp)of CVA16 emerges as a promising drug target for HFMD treatment.This study presents an in-silico pipeline for the identification of potential RdRp inhibitors against CVA16.A library of 91 natural compounds derived from Bacopa monnieri(brahmi)was virtually screened against the CVA16 RdRp.Here,Bacobitacin D emerged as a promising hit molecule,forming 8 hydrogen bonds including key catalytic site residues(Asp^(238)and Asp^(329))within the RdRp active site.Further,molecular dynamics(MD)simulations and MM/GBSA binding free energy calculations was applied on the top three hits that were selected based on exhaustive docking scores(≤-9.55 kcal/mol).Bacobitacin D exhibited sustainable stability,as evidenced by minimal deviation(RMSD=0.75±0.02 nm)during a 100 ns MD simulation.Importantly,Bacopaside IV exhibited the lowestΔGTOTAL binding free energy(-23.70 kcal/mol),while Bacobitacin D displayed a comparableΔGTOTAL of19.14 kcal/mol.Structural interpretation of the most populated cluster derived from MD simulations showed direct interactions of Bacobitacin D with pivotal catalytic residues,including Asp^(238)and Ser^(289).This comprehensive study confirmed Bacobitacin D as a potent inhibitor of CVA16 RdRp,offering a potential avenue for therapeutic intervention against HFMD.Experimental validation is required to confirm the inhibitory action of Bacobitacin D against HFMD.

Gaseous plume flows in space propulsion

This paper presents a gaskinetic study on high-speed, highly rarefied jets expanding into a vacuum from a cluster of planar or annular exits. Based on the corresponding exact expressions for a planar or annular jet, it is convenient to derive the combined multiple jet flowfield solutions of density and velocity components. For the combined temperature and pressure solutions, extra attention is needed. Several direct simulation Monte Carlo simulation results are provided to validate these analytical solutions. The analytical and numerical solutions are essentially identical for these high Knudsen number jet flows.