Enzymes are biological molecules which catalyzes all vital biochemical reactions that happens within cells. These excellent biological catalysts are very precise and efficient. It is interesting to know how these enzymes are so efficient and what cause the malfunctioning enzymes (leads to many diseases). Without accurate representation of an enzymatic environment in computer simulation, it is impossible to get these answers. Any comprehensive molecular understanding of chemical processes happen inside enzymes is required. This realization leads to the development of methods that paved the way for quantitative studies of enzymatic reactions . This work introduced the hybrid Quantum mechanical/Molecular mechanics (QM/MM) method and a microscopic dielectric model that have represented entire enzyme-substrate complex in solution. This facilitated the first consistent modeling of the catalytic effect of an enzyme. Researchers has embraced this idea of representing the enzymatic reactions and continue to work in the betterment of our understanding about enzymes.
Our group starting from the development of the first consistent modeling of the catalytic effect of an enzyme, has continued to lead the field by further developing QM/MM methods, including the powerful Empirical Valence Bond (EVB) approach, simulating the dynamics of enzymatic reactions and introducing the use of free energy perturbation methods to such reactions. These studies clarified the relationship between reactions in solution and enzymes and established the catalytic role of pre-organized active sites. Our current studies continue focusing on: