Publication of the week: Professor Paul Finn

6 October 2014

G. Lauro, N. Ferruz, S. Fulle , M.J. Harvey, P.W. Finn & G. De Fabritiis, “Reranking docking poses using molecular simulations and approximate free energy methods”, Journal of Chemical Information and Modeling 54.8 (2014),  2185–2189. DOI: 10.1021/ci500309a.

Computational modelling techniques have become well-established as one of the standard methods used in the design of new drugs and in silico virtual screening of large chemical compound databases against protein drug targets is now routinely used in the early stages of the drug discovery process.

Although there are many examples of successful application, obtaining an effective compromise between computational cost and quality of results remains a challenge in the development of universally applicable virtual screening methods. Limitations of the current methods include limited modelling of the flexibility of the system, and simplified treatment of the aqueous medium in which the interactions take place.

In this study, we have compared the effectiveness of the theoretically more rigorous, but computationally more expensive, linear interaction energy (LIE) method, against standard docking approaches. Although the capabilities of the LIE method have been extensively tested in the past, probing its suitability as a high-throughput virtual screening tool is still relatively new because the computational power necessary has only recently become widely available.

Using a set of 1,549 compounds, we performed a total of 12,250 simulations. The LIE method proved effective but did not yield results significantly better than those obtained with docking codes. To facilitate further research in this area, the entire database of simulations is made publicly available.


Professor Paul Finn is Professorial Research Fellow in the Clore Laboratory and Department of Applied Computing. He is also CEO of InhibOx, a spin-out company from the Chemistry Department of the University of Oxford focused on computer-aided drug design, and runs a drug design consultancy Affinity Drug Design.