Improved residue contact prediction using support vector machines and a large feature set

Abstract

Background: Predicting protein residue-residue contacts is an important 2D prediction task. It is useful for ab initio structure prediction and understanding protein folding. In spite of steady progress over the past decade, contact prediction remains still largely unsolved.

Results: Here we develop a new contact map predictor (SVMcon) that uses support vector machines to predict medium- and long-range contacts. SVMcon integrates profiles, secondary structure, relative solvent accessibility, contact potentials, and other useful features. On the same test data set, SVMcon's accuracy is 4% higher than the latest version of the CMAPpro contact map predictor. SVMcon recently participated in the seventh edition of the Critical Assessment of Techniques for Protein Structure Prediction (CASP7) experiment and was evaluated along with seven other contact map predictors. SVMcon was ranked as one of the top predictors, yielding the second best coverage and accuracy for contacts with sequence separation > or = 12 on 13 de novo domains.

Conclusion: We describe SVMcon, a new contact map predictor that uses SVMs and a large set of informative features. SVMcon yields good performance on medium- to long-range contact predictions and can be modularly incorporated into a structure prediction pipeline.

Figure 1

3D Structure of Protein 1DZOA. Protein 1DZOA is an a+b protein. It consists of two alpha helices and two beta sheets. Beta strands 1 and 2 form a parallel beta sheet. Beta strands 3, 4, 5, 6 form an anti-parallel beta sheet. Most non-local contacts involve the pairing interations between beta strands and the packing interactions between helices and beta sheets. (Figure rendered using Molscript [63]).

Figure 2

Predicted and True Contact Maps of 1DZOA. The upper triangle shows the true contacts of protein 1DZOA. The lower triangle shows the predicted contacts of protein 1DZOA. 2L (240) top ranked contacts are selected. The key contacts within anti-parallel strand pairs (3,4), (4,5), and (5,6) are recalled. A few contacts within the parallel strand pair (1,2) are also predicted correctly. However, very long range contacts between alpha helices and beta sheets are not predicted. And there are some false positives. It is interesting to see that most false positives are close to the true contacts. Thus, they may not be very harmful when being used as distance restraints to reconstruct protein 3D structure.