The design of new drug-like small molecules that bind to a disease-involved protein with high affinity and specificity is a crucial goal in pre-clinical drug discovery. Computational methods that accurately predict free energies of binding could significantly reduce the costs of drug discovery. However, it remains challenging to routinely predict free energies of binding. There are different reasons for this. For example, the binding affinity is the sum of numerous enthalpic and entropic contributions that cannot be broken down into functional group components and are difficult to quantify by using only static structural models of protein-ligand complexes(1). In principle, molecular simulations methodologies can compute free energies of binding but improved analysis and sampling algorithms are necessary to compute well-converged binding free energies. We are calculating binding affinities in several different biomolecular systems using a variety of simulation protocols, and will report on our findings in terms of efficiency and predictive power of the calculations. A comparison between experimental and predicted data will also be presented. References 1. Freire, E. Drug Discovery Today, 13, 869–874, 2008

Investigation of binding affinity in bio-molecular complexes

251st National Meeting (2016)

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