Identifying patterns of conformational changes in HLA-A*0201-related immunological activities

Key to adaptive immune response is the recognition of HLA/peptide complexes by a particular T-cell receptor, which obviously is preceded by HLA binding of the antigenic peptides. Extreme polymorphism of the HLA gene has claimed exhaustive revelation of the possible (TCR-)HLA/peptide interactions to be intractable should it be based on the wet-lab experiments alone. Sequence-based and structure-based predictors have since been developed to allow researchers perform the wet-lab experiments selectively on the potential candidates that have previously been predicted to elicit some immunogenic activities. Structure-based predictors, which often include the use of molecular simulations and the concept of association as well as dissociation energy, are generally unsuited for high-throughput screening despite ability of these predictors to generate more accurate prediction results. As the binding and recognition process occurs, new inter-atomic interactions are introduced—suggesting conformational changes are really anticipated. Nonetheless, only parts of the constituents shall experience structural changes. It is therefore desirable that all the substantial regions around which conformational changes are likely to happen be identified. The internal coordinates—i.e. the bond lengths, the bond angles, as well as the torsion angles—of the HLA-A*0201 were analyzed in this work before and after the binding and recognition process took place. The findings can hence be used as a guide to decide the flexibility of the molecules in the molecular simulations. For many of them, it is common to treat the whole receptor as rigid and the whole ligand as flexible since fully flexible receptor could incur huge computational cost. Semi-flexible receptor, therefore, could yield better accuracy yet maintain computational cost within reasonable limit.