Nature has engineered enzymes to catalyse nature itself. Enzymes are used to produce drugs as an alternative to the chemical synthesis to reduce cost, to improve stereo selectivity, overcome practical concerns like high temperature and pressure and to make the process eco-friendly. Designer enzymes mimicking evolution on a laboratory timescale is the trend in the global enzyme market.
Conventional methods such as Rational Design and Directed Evolution for enzyme modification depend on re-sampling and in vitro confirmation studies, which make them time-consuming and costly exercises. The advent of computational methods has, to a large extent, unveiled the complexity of enzymatic reactions. Methods like QM/MM, REMD, Transition state path sampling, to name a few, provides accurate atomistic picture and reasonable information on the thermodynamics of enzymatic reactions.
We have developed a “Core Work Bench”, underlying which is the QM/MM protocol and engineers the given enzyme for a specific outcome. The method was used to engineer cellulase, protease and transaminase to improve the kinetic properties and enantio-specificity.