Question

Computer simulations that use only classical mechanics (Newton’s Laws, pre-quantum equations, etc) can be used to simulate protein folding, drug binding, etc. But, classical mechanics-based computer simulations CANNOT be used to predict enzyme reactions because these involve breaking and forming covalent bonds, which involves redistributing electron orbitals around molecules.

Explain why Quantum Mechanics-based computer simulations are needed to accurately simulate enzyme reactions.

Answer 1

Understanding the action of enzymes on an atomistic level is one of the important aims of modern biophysics and it needs an accurate and computationally efficient energy function. Therefore, quantum mechanics is essential for modeling of mechanism and kinetics for small molecules like enzyme because - (i) electronic structural theory is needed to calculate the necessary potential energy surface for the enzyme system to adequately treat the bond forming and breaking processes, (ii) quantum mechanical treatment of vibrational motions allows to more accurately estimate the rate constant for enzyme reactions, (iii) consideration of nuclear tunneling to understand enzyme mechanism and the transition state through quantitative computation of kinetic isotope effects.