Protein - ligand interactions from a quantum fragmentation perspective : the case of the SARS-CoV-2 main protease interacting with α−ketoamide inhibitors
Résumé
We present a hybrid, multi-method, computational scheme for protein/ligand systems well suited to be used on modern and forthcoming massively parallel computing systems. The scheme relies on a multi-scale polarizable Molecular Modeling, MM, approach to perform MD simulations and on an efficient DFT Linear Scaling method to post-process simulation snapshots. We use this scheme to investigate recent α-ketoamide inhibitors targeting the main protease of the SARS-CoV-2 virus. We assessed the reliability and the coherence of the hybrid scheme in particular by checking the ability of MM and DFT to reproduce results from high-end ab initio computations regarding such inhibitors. The DFT approach enables an a posterior fragmentation of the system and an investigation into the strength of interaction among identified fragment pairs.