I am interested in understanding the three-dimensional structure of proteins. This breaks down into three main research areas. All of these areas are investigated using computational methods.
Faculty of Life Sciences, University of Manchester
E-mail: simon.lovell@man.ac.uk, (contact address).
Research Interests
I am interested in understanding the three-dimensional structure of proteins. This breaks down into three main research areas. All of these areas are investigated using computational methods.
Protein structure is determined by the linear sequence of amino acids. This amino acid chain rapidly folds up in the cell, giving rise to complex three-dimensional structures. For most proteins it is this three dimensional structure which determines how proteins function in the cell.
Unfortunately, we do not know the details of why proteins fold as they do, nor how the sequence determines the structure. I hope to gain insights into these relationships by analysis of protein structures, and the development of physics-based rules that can be used to predict protein structure.
Protein structure is generally more conserved than sequence, because of
the intimate relationship between structure and function. The maintenance
of function is strongly selected for evolutionarily, and so this place
restraints on protein structure. Just as the sequence of a protein gives
rise to the structure, the structure places evolutionary restraints on the
sequence. By understanding these restraints we can understand how structure
evolves over time, how one structure can give rise to another, and we can
predict structure using evolutionary information.
The strongest evolutionary restraints on a protein are in the functional sites, for example the active site of an enzyme. We can use our knowledge of protein structure and the evolutionary restraints on it to identify functional sites, binding sites, oligomerisation sites and protein-protein interaction sites. We would like to be able to use this information to identify protein function directly. This is particularly important at the moment, given the wealth of sequence data from the various genome-sequencing projects and the structural data from structural genomics projects. This data must be turned into usable biological information if most use is to be made of it.
PhD Positions I am hoping to have PhD positions available to start in September 2004. If you are interested, you should apply through the School's central application procedure. Details can be found here.
Publications (link to pubmed).
Teaching Kinemages