Research And Evaluation Of Environmental Specific Precise Force Field ESFF1

With the development of super computer,Molecular simulations has been playing an important role in research of structure-function relationship of macro-biomolecule,novel drug targets searching,and drug optimization.However,with the discovery of disease associated intrinsically disordered proteins(IDPs),which have very high flexible conformers and hardly researched by traditional experimental approach,the demand on precise computational tool and molecular dynamics simulation is increasing.Recently,molecular dynamics simulation that base on force field method and conformers' sampling algorithm have been significantly developed for IDPs modeling.However,most of recent IDPs specific force fields are weak in reproduce accurate structural feature of IDPs.Here,we present an environmental specific precise force field called ESFF1 to increase the accuracy of IDPs modeling and refine structures for disease associated IDPs.As the original version,the chemical attributions of neighbor residues were taken into consideration and distinguished torsional parameters were trained for a same residue at four different neighbor environments.A series of tests of 14 structured proteins,46 short peptides,15 disordered proteins,2 ordered-disordered protein complexes,and 6 fastfolding proteins show that the simulation predicted NMR properties such as J-coupling,order parameters and chemical shifts of C?,C?,C',N,H?,and HN are exactly in accord with corresponding experimental measurements.The ESFF1 achieved a balance between excessive order of ff14 SB and excessive disorder of ff14 IDPSFF,which significantly improved the conformer sampling of IDPs.With the improved accuracy and efficiency of protein modeling,ESFF1 is also able to reproduce thermodynamic properties that revealed by different experimental methods in REMD of fastfolding proteins.