Investigating The Interaction Between Biomolecules Via Molecular Dynamics Simulation

Biomolecules play crucial roles in life activities.The interaction between biomolecules is the molecular basis of biological functions.Deciphering the molecular mechanisms of interaction between biomolecules can provide critical clues to understand biological functions of biomolecules.Besides that it also provides an essential basis of drug design for disease-related biomolecular.The investigation on the interaction between biomolecules in this article includes the following two aspects:(1)Using molecular dynamics simulation to investigate the process of CXXC domain recognition of CpG sites,to clarify the molecular mechanism of residue mutations regulating the function of CXXC domain.(2)Using molecular dynamics simulation to evaluate the feasibility of utilizing implicit solvent models to investigate intrinsically disordered proteins,which provides the solid foundation for the investigation of oligomers formed by intrinsically disordered proteins.The detailed information is listed as follows:(1)The molecular mechanism of specific recognition of CpG sites by CXXC domain.The CXXC domain is a zinc finger protein that specifically recognize CpG sites in DNA.The recognition between CXXC domain and CpG sites might induce serious diseases like mixed-lineage leukemia.Experimental studies have shown that mutating C11 88 to D11 88 in CXXC domain inhibits its ability to recognize CpG sites,but the molecular mechanism is still unclear.We used molecular dynamics simulation to investigate the recognition between CXXC domain and CpG sites.We found that C1188D mutation induced the bending of the N-terminal of the CXXC domain,which prevented it from forming stable encounter complex with DNA,thus inhibiting the specific recognition of CpG sites by the CXXC domain.A two pathway model of the recognition process was put forward based on our simulation results.(2)Evaluation of implicit solvent models for simulating intrinsically disordered proteins.Intrinsically disordered proteins(IDPs)are proteins that cannot form stable three-dimensional structure in physiological conditions.Various studies have demonstrated that oligomers formed by IDPs are closely related to serious diseases like diabetes,Alzheimer's disease and Parkinson's disease.In order to explore the feasibility of implicit solvent models for the study oligomers of IDPs.We evaluated GBHCT?GBOBC??GBOBC??GB-Neck and GB-Neck2 implicit solvent models using peptide GGXGG as model system.The results indicated that GBOBC? was the most suitable implicit solvent models to describe the GGXGG system.However,current implicit solvent still need further improvements:1)In all the implicit solvent models tested,the X residue of GGXGG was more inclined to form the ?-sheet structure.2)The retention probability of implicit solvent models were much lower than that of explicit solvent models.