| Title: |
Fast dynamics perturbation analysis for prediction of protein functional sites |
| Authors: |
Ming, Dengming; Cohn, Judith D; Wall, Michael E |
| Publisher Information: |
BioMed Central Ltd. |
| Publication Year: |
2008 |
| Collection: |
BioMed Central |
| Description: |
Background We present a fast version of the dynamics perturbation analysis (DPA) algorithm to predict functional sites in protein structures. The original DPA algorithm finds regions in proteins where interactions cause a large change in the protein conformational distribution, as measured using the relative entropy D x . Such regions are associated with functional sites. Results The Fast DPA algorithm, which accelerates DPA calculations, is motivated by an empirical observation that D x 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. Conclusion 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
http://www.biomedcentral.com/1472-6807/8/5 |
| Availability: |
http://www.biomedcentral.com/1472-6807/8/5 |
| Rights: |
Copyright 2008 Ming et al; licensee BioMed Central Ltd. |
| Accession Number: |
edsbas.83FD824 |
| Database: |
BASE |