Epoch-Making Simulation Analysis of Mutation Mechanisms of Influenza Virus Based on the Fragment Molecular Orbital Method Project

On the basis of the fragment molecular orbital (FMO) method, we performed the FMO-MP2 and FMO-MP3 electronic-state calculations on the Earth Simulator (ES2) for a protein complex consisting of HA (hemagglutinin) trimer and two Fab fragments and a complex of NA (neuraminidase) and oseltamivir inhibitor of influenza virus. The FMO-MP2/6-31G jobs were completed in 0.8 hours for the HA monomer and in 4.3 hours for the HA trimer with 128 nodes (1024 VPUs) of ES2. Comparison of these timings illuminates the low scaling nature of the present FMO calculations. In addition, the increase rate of computational cost by MP3 compared to MP2 is significantly low. In particular, the FMO-MP3 calculation for the HA trimer, which might be the world's largest target system (36160 atoms) for correlated all-electron calculations to date, was completed in only 5.8 hours with 128 nodes. In the case of NA-oseltamivir, a favorable performance of FMO-MP3 calculation was obtained as well. Thus, a realistic applicability of FMO-MP3 calculations to large-scale proteins has been demonstrated with the ES2 system. Molecular interaction analyses based on the FMO results were then carried out for the prediction of probable mutations in influenza proteins associated with the escape from antibody pressure and the resistance against drugs.