%0 Journal Article
%T Fast dynamics perturbation analysis for prediction of protein functional sites
%A Dengming Ming
%A Judith D Cohn
%A Michael E Wall
%J BMC Structural Biology
%D 2008
%I BioMed Central
%R 10.1186/1472-6807-8-5
%X The Fast DPA algorithm, which accelerates DPA calculations, is motivated by an empirical observation that Dx in a normal-modes model is highly correlated with an entropic term that only depends on the eigenvalues of the normal modes. The eigenvalues are accurately estimated using first-order perturbation theory, resulting in a N-fold reduction in the overall computational requirements of the algorithm, where N is the number of residues in the protein. The performance of the original and Fast DPA algorithms was compared using protein structures from a standard small-molecule docking test set. For nominal implementations of each algorithm, top-ranked Fast DPA predictions overlapped the true binding site 94% of the time, compared to 87% of the time for original DPA. In addition, per-protein recall statistics (fraction of binding-site residues that are among predicted residues) were slightly better for Fast DPA. On the other hand, per-protein precision statistics (fraction of predicted residues that are among binding-site residues) were slightly better using original DPA. Overall, the performance of Fast DPA in predicting ligand-binding-site residues was comparable to that of the original DPA algorithm.Compared to the original DPA algorithm, the decreased run time with comparable performance makes Fast DPA well-suited for implementation on a web server and for high-throughput analysis.Prediction of protein functional sites is a key aspect of protein function prediction [1], and can be an important step in identifying small-molecule interactions for drug discovery [2]. It can also potentially be used as a pre-processing step to reduce the search space in computational docking algorithms. There are many methods to predict functional sites¨Chere we emphasize those that make use of analysis of protein structure and dynamics. Existing protein structure analysis methods are based on diverse principles, including: association of functional sites with surface clefts that have ex
%U http://www.biomedcentral.com/1472-6807/8/5