Evaluation of the binding affinity of antibodies from antigen binding energy and V_H-V_L interaction energy calculated by the MM-GBSA method

摘要

Because antibodies are a kind of proteins having high affinity and specificity for antigen,they are expected to be suitable candidates for drugs which have more efficient and less side effect than conventional chemical drugs.In fact,the increasing number of biopharmaceutical drugs are now available or on trial.To support the developments of these drugs,rapid and highly accurate screening is indispensable.In silico screening is one of powerful solutions to this purpose.In this study,we performed molecular dynamics simulation of antibody HyHEL-10 and its antigen white hen egg lysozyme(HEL)to collect the trajectories of binding structures.After MD simulation,we have executed the molecular mechanics-Generalized Born surface area(MM-GBSA)method to evaluate the binding affinity between HyHEL-10 and HEL.Antigen binding energy calculated with the MM-GBSA method is partially incompatible with the changes in free energy measured by isothermal titration calorimetry(ITC).The variants mutated in the light chain (LS91A,LS93A,LY50F)show less satisfactory result than the variants mutated in the heavy chain(HD32A,HD96A,HD32AD96A).To resolve the discrepancy between the experimental and the computational results,we have also calculated interaction energy between antibody heavy chain variable region flagment(VH)/antibody light chain variable region flagment(VL)with MM-GBSA.Combination of these two calculated energy shows better correlation with the experimental results than the respective energy.