Title Comparative Study On CD4-dependent And CD4-independent Molecular Dynamics Simulations Of Protein Unfolding Based Upon HIV-1 Gp120 By High-temperature Molecular Dynamics Simulations

Most HIV-1 virus infection to the cells of our bodies need the virus package is sugar protein gp120 combined with human CD4 receptor molecules on the cell membrane,but also have some virus without HIV-1 in combination with CD4 can infect cells.According to the dependence of gp120 on CD4,the gp120 was divided into two types:CD4 dependent gp 120 and CD4 independent gp 120,What are the differences between the two types of gp120?In order to shed light on the differences in conformational conversion capacity of CD4 dependent gp120 and CD4 independent gp120,our thesis mainly through the constructing crystal structure model of two types of unbound in gp120 state and simulating the unfolding process of protein with high temperature.Based on the selection of the CD4 dependent and non-cd4 dependent hiv-1 gp120 amino acid sequence,the gp120 structure from the closure of the closed state of the envelope was used as a template;Comparative study of the crystal structure model of CD4 dependent gp120 and CD4 independent gp120 under the condition of unbound was constructed by homology modeling,Comparative study of the crystal structure model of CD4 dependent gp120 and CD4 independent gp120 under the condition of unbound was constructed by homology modeling,in this part of the study,molecular dynamics simulations were performed at high temperatures(300,473,573 and 673 K).Comparative study of CD4 dependent gp120 and CD4 independent gp120 by high temperature molecular dynamics simulations.We compare difference of geometrical properties,secondary structure,unfolding rate,and path,flexibility and two-dimensional conformational sub-space etc.The result show that:(1)When the temperature is higher than 300 K,CD4 dependent gp120 exhibits greater structural fluctuations,more unstable secondary structures and higher global conformational flexibility than CD4 independent gp120.(2)Despite the two proteases have similar fold path,but at high temperature under the same condition,CD4 independent gp120 has unfolding rate faster than the CD4 dependent gp120,Leading to the end of the simulation of the former than the latter has a greater degree of denaturation;(3)In three high temperature condition,CD4 independent gp120 showed more largerd radius of gyration and less more number of intramolecular hydrogen bond and number of close interatomic contacts,more number of protein solvent hydrogen bond and solvent apolar surface area than CD4 dependent gp 120.(4)in the first two eigen vector consisting of two dimensional subspace in nature,the CD4 dependent gp120 covered by sampling area is more extensive than CD4 steroid-dependent gp120,means that the former than the latter has more conformational state or child;At the same time,in the first described the molecular motion of eigen vector,the CD4 dependent gp120 than CD4 dependent gp120 showed more significant fluctuations.The results show that the CD dependent gp120 than CD4 dependent gp120 conformation with lower thermal stability and higher flexibility,it is because of the CD4 dependent gp120 high conformational flexibility,to be more significant than the CD4 steroid-dependent gp120 large-scale collaborative movement or more conformation sub-state,and more conformation sub-state increased gp120 for auxiliary receptor CCR5(CXCR4)for selective combination of opportunity,this explains why the CD4 dependent gp120 can under the condition of lack of CD4 receptor infected human cells.In addition,for the CD4 dependent gp 120 and CD4 dependent gp120,the former more conformational flexibility is probably because it has less in non covalent interaction in the molecular and more protein-(intermolecular interactions between solvent,and CD4 dependent gp120 high stability can be attributed to its more non covalent interaction in the molecule and the closer the structure of the packaging.Our results provide insight into the differences in conformational conversion capacity of CD4 dependent gp120 and CD4 independent gp 120,and facilitate understandings of the conformational contral mechanism of HIV-1 gp120.At the same time also made clear the CD4 dependent from the perspective of structural dynamics and CD4 dependent gp120 receptor dependent on the molecular basis of differences behind.