Solution Conformations Of Large Biomolecules Investigated By Molecular Dynamics Simulations Using New Force Field And Water Models

The study of conformations of biomolecules in solution has always been an important issue.As complementary to experimental methods tools including small angle x-ray scattering,NMR,Cryo-EM and molecular dynamics(MD)simulation can be useful to study.Moreover,computational simulation is also usful to study solution conformations.Molecular dynamics simulation can find the low energy state and molecular mechanism during the lifetime of biomolecules in solution.Though there are some drawbacks of computational simulation,the precision of the force fields and the sampling of the simulation regard as two big difficulties in the field of molecular dynamics simulation.In this paper we used the new force field and the water model,RSFF2+/Tip4p-D,to run the all-atom molecular dynamics simulation targeted on T4 lysozyme,which could improve the sampling during the simulation.Then we fitted the result of the simulation to the result of the small angle x-ray scattering data.We also tried method of the calculation of the free energy,WHAM(Weighted Histogram Analysis Method).The reason we chose T4 lysozyme as the target was that its structural properties,which has a mouth contains 2 subdomains and a link consisted by a long alpha helix.The open or close of the state decides its biological activity.For making sure this force field and water model can fit more protein systems,we used it to target on Hfq as well as fitted the small angle x-ray scattering data of Hfq.Hfq's conformation is like an alpha helix circle with 6 protein tails,these 6 tails stretch and coil during their biological lifetime.The other target we have worked on is that nucleosome.The molecular mechanism of assembling of nucleosome and the combination of nucleosome and DNA have been 2 big problems for researchers for many years,but the veil of dynamics of them have not been really revealed.We used all-atom molecular dynamics simulation to run on 4 monomers,2 dimers,a tetramer and an octamer of the nucleosome.We also used accelerated molecular dynamics simulation(aMD)and coarse-grained molecular dynamics simulation for searching and reaching more possible structural conformations as well as providing more details of dynamics process and molecular mechanisms.