Radical, force-driven computational methods for enzyme design in biotechnology

Enzymes offer enormous promise in the cost-efficient, environmentally friendly production of existing and new molecules. One of the most challenging areas in chemical biology, however, is the very design of new enzymes. Computer simulation is particularly suited to enzyme design because it provides detailed molecular insight that is crucial for any rational design process. And one of the most rapidly growing areas in science happens to be computer simulation. This is because of the ever-growing scale of computers and the development of powerful new algorithms.

The Principal Investigator of this project, Dr Henchman, has recently pioneered two new such algorithms that solve major technical challenges in applying computational methods to any system. One algorithm quantifies the vibrational flexibility of any molecule using the force acting on the molecule, something that previous algorithms could only do for relatively rigid systems. The other algorithm, termed RAD, is a general, truly predictive way to determine atomic coordination for any molecular system, not just for bonded atoms but more importantly for non-bonded coordination. The scope of both algorithms is immense and they provide a key way to quantify molecular stability. In this project, they will be leveraged to guide enzyme design, together with the Nobel-prize winning quantum mechanics/molecular mechanics methodology to study enzyme kinetics. All research will take place in the world-leading Manchester Institute of Biotechnology which will provide opportunities to test your predictions.