Details of Grant 

EPSRC Reference:	GR/R24753/01
Title:	Novel Computational Approaches To the Understanding and Prediction of Protein-Ligand Interactions
Principal Investigator:	Mitchell, Dr J
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department:	Chemistry
Organisation:	University of Cambridge
Scheme:	Fast Stream
Starts:	01 October 2001	Ends:	30 September 2004	Value (£):	59,557
EPSRC Research Topic Classifications:	Chemical Biology Protein chemistry
EPSRC Industrial Sector Classifications:	Pharmaceuticals and Biotechnology No relevance to Underpinning Sectors
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Panel History:
Summary on Grant Application Form
The project addresses the prediction, design, evolution and energetics of protein-ligand interactions. The vision is to develop a systematic and detailed understanding of protein-ligand binding that will feed into molecular design, particularly in the pharmaceutical context. We will prepare a database of protein-ligand interactions containing chemical, biochemical and bioinformatics data, with links to available three-dimensional structures. This will include binding constants, structural classification of proteins, ligand structures, biological functions and crystallisation conditions. We will study the relationships between the sequence and structural similarities of proteins and the molecular similarities of the ligands they bind. The results will initially be represented as plots of protein-protein vs. ligand-ligand similarity for all pairs of protein-ligand complexes in the dataset. We will investigate whether there are significant differences between datasets where (a) the protein-ligand binding is a product of evolution; (b) the protein-ligand binding is a product of rational design; (c) the protein-ligand binding is non-biological. We will carry out detailed profiling of protein-ligand complexes in terms of the relative usage of different interaction types such as hydrogen bonds, other polar interactions, hydrophobic-hydrophobic contacts and polar-hydrophobic ('mixed') interactions such as N-H..pi and C-H..O. This will allow us to investigate the conserved and variable aspects of protein-ligand binding. We will investigate whether complexes cluster into distinct types, based on their usage profiles, or whether they form a continuous distribution.
Key Findings
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Potential use in non-academic contexts
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Organisation Website:	http://www.cam.ac.uk