Molecular Modelling Group

Every living organism is a biological industry where every second a biochemical reaction occurs, which is catalysed by some enzymes. We eat, drink, sleep, breath, digest food, all are biochemical reactions, and certain enzymes are responsible for this. The catalytic activity of these naturally occurring enzymes are very complex and challenging for the experimental and theoretical chemists to study. Moreover, the structural and electronic properties, as well as reactivities of naturally occurring metalloenzymes, are much more complicated because of the involvement of various spin states of the metal. Therefore, our group is focusing on exploring the intricate reaction mechanism of these transition metal-based metalloenzymes, specifically, non-heme high-valent FeIV-oxo dependent ones. We try to understand the mechanism of the metalloenzymes, which are capable of performing very intriguing organic transformations and utilising the mechanistic insights to design novel bio-mimic catalyst which are efficient and robust for the desired reactions. In this direction, our concentration is centred on the detailed structural, electronic, and spectral property studies of these systems along with the investigation of the role of various spin states on the reaction mechanism. For this purpose, firstly, we understand the energetics of formation, structure and bonding aspects of various possible intermediates and transition states through the quantum mechanical study of the small active site models. Secondly, a study on more realistic entire metalloenzymes using combined Quantum mechanics and molecular mechanics (QM/MM) method which would give information on the importance of protein environment and solvent hydrogen bonds on the reaction mechanism. Eventually, these studies put together would help us in understanding the reaction mechanism with good accuracy and subsequently make predictions and suggestions for the experimental studies.



Figure: The active site (QM) of the naturally occurring halogenase metalloenzyme while the remaining part has shown as MM part.

QM/MM method is fascinating nowadays and also advantageous as it combines the accuracy of quantum mechanics and the speed of molecular mechanics. The active site of the metalloenzyme is used as the QM part and the remaining as the MM part. The small model and the QM region is treated by Density Functional Theory (DFT) method, and the MM part is described by the classical AMBER force field method. We are using AMBER16 for the classical molecular dynamics simulation, ONIOM method implemented in Gaussian09 for the QM/MM study. Recently we have started using ChemShell interface combining ORCA 4.0.1 for the QM part and DL_POLY for the MM part. For the spectral properties, we are using ORCA 4.0.1 software. In the given picture we have shown a structure of naturally occurring halogenase metalloenzyme, where the QM part has shown as ball and stick model where the remaining grey-coloured portion in cartoon form is the MM region.