MRC DTP 4 Year PhD Programme: Binding Affinity Prediction in Drug Discovery

The major challenge in drug discovery is to develop a compound that is capable to interact with a biological target associated to the disease and has a good balance of physical and biological properties necessary to become an efficacious and safe drug. One of the key aspects that needs to be optimized in this process is the “binding affinity” that represents the strength of interaction between the compounds (ligand) and the biological target (protein). The possibility to accurately predict in silico the binding affinity of compounds against the biological target could enhance the design-make-test cycle typical of the compound optimization process and help focus the medicinal chemists synthetic work on the most promising molecular targets.
Several methods to estimate interaction energies between molecules have been developed in the past but due to the high computational requirements have been confined to study interactions between small molecules. Given the recent advances in computing resource, we are now in a position to be able to consider the use of computational methods to calculate the binding affinity of ligands for larger biological systems (ligand:protein complexes).
Working within the Drug Discovery Unit, Computational Chemistry group the student will develop the application of different computational methods like Quantum Mechanics (QM), Fragment Molecular Orbitals (FMO) and Free Energy perturbation (FEP) in the context of active Drug Discovery programs