Relationship between protein structure and function: Valuable insight from computational studies

Life as we know it is sustained by the plethora of functional roles performed by proteins -- the precise function depending exquisitely on three-dimensional structure. The quest to understand protein function from structure has led worldwide to the establishment of a number of structural genomics projects and the concomitant substantial investment from both the public and private sectors, estimated to total around US$1 billion worldwide. Once a structure is solved, deducing function on the basis of this structure alone is often a non-trivial, but nonetheless essential, exercise -- mankind's pursuit of a complete, working molecular model of a cell is underway. This article discusses some of the computational approaches that assist in: (i) deducing function from protein structure, and (ii) elucidating factors at the atomic level that determine function. Far from replacing experimental studies, these approaches should be used to complement them -- the real value comes from an interdependent multidisciplinary approach.