Exploring The TCR-pMHC1 Protein-Protein Interaction In Living Organisms

Protein-Protein interactions(PPIs)are important events that occur all the time in the life of an organism.The transmission of biological information,the expression of genetic information,the control of genes,the role of enzymes,the production and consumption of energy,apoptosis,and disease-related(cellular immunity).The study of PPIs can understand the function of proteins from the molecular level and explain the laws.The normal interaction of PPIs can guarantee the healthy operation of living organisms,and the blocked interaction of protein proteins can cause diseases in the body.The current research on PPIs has promoted human research on diseases.At present,the recognition mechanism of TCR recognition pMHC is not very thorough.We used the research group’s newly improved computational alanine scanning(CAS)to predict hotspot residues to explore the TCR-PMHC1 protein protein interaction.This also provides us with a viable way to explore the inside of protein proteins.We used the role of entropy and the calculation of specific residues of MM/GBSA as a method of binding energy contribution.In the traditional MM/PBSA calculation combined with free energy,the entropy calculation method is the normal mode calculation combined with free energy.The method is rigorous,but the calculation is expensive and inefficient.We calculate the entropy(-TΔS)directly on the basis of molecular dynamics.The calculation speed is fast and the value is stable.After verification,the contribution of entropy is introduced,and the calculated value is closer to the experimental value.In our method,the hotspot is predicted by changing the residue to alanine,and then the difference in binding energy between the two systems is calculated.Here we only use a trajectory generated from the MD process to calculate the original binding energy.Calculate the binding binding energy.The C_γatom is replaced with a hydrogen atom in the same direction as C_β-C_γ,and the bond length is set to a default value according to the molecular model used to obtain a mutation trajectory.Thus the backbone remains,and the energy contribution of the backbone can be eliminated before and after the mutation.Therefore,the energy difference before and after the mutation mainly comes from the side chain.After the mutation,we can calculate the binding energy of the mutation.This method has been elaborated in our previous work.On this basis,this paper selects four classic TCR-pMHCI systems as research objects,which are divided into two groups,two of which are derived from mice and the other two are derived from humans.The systems of these two groups have similarities.They have the same MHC,the same TCR,but the peptides are different.These four systems were chosen because these four systems are classic systems in the field of immunization,and a large number of studies are based on these four systems.Our calculations indicate that CDR loops have interaction and specificity for peptide/MHC recognition.