Yifeng David Yang

Background: Protein-protein interactions are a pivotal component of many biological processes and mediate a variety of functions. Knowing the tertiary structure of a protein complex is therefore essential for understanding the interaction mechanism. However, experimental techniques to solve the structure of the complex are often found to be difficult. To this end, computational protein-protein docking approaches can provide a useful alternative to address this issue. Prediction of docking conformations relies on methods that effectively capture shape features of the participating proteins while giving due consideration to conformational changes that may occur. Results: We present a novel protein docking algorithm based on the use of 3D Zernike descriptors as regional features of molecular shape. The key motivation of using these descriptors is their invariance to transformation, in addition to a compact representation of local surface shape characteristics. Docking decoys are generated using geometric hashing, which are then ranked by a scoring function that incorporates a buried surface area and a novel geometric complementarity term based on normals associated with the 3D Zernike shape description. Our docking algorithm was tested on both bound and unbound cases in the ZDOCK benchmark 2.0 dataset. In 74% of the bound docking predictions, our method was able to find a near-native solution (interface C-α RMSD ≤ 2.5 Å) within the top 1000 ranks. For unbound docking, among the 60 complexes for which our algorithm returned at least one hit, 60% of the cases were ranked within the top 2000. Comparison with existing shape-based docking algorithms shows that our method has a better performance than the others in unbound docking while remaining competitive for bound docking cases. Conclusion: We show for the first time that the 3D Zernike descriptors are adept in capturing shape complementarity at the protein-protein interface and useful for protein docking prediction. Rigorous benchmark studies show that our docking approach has a superior performance compared to existing methods.

Background: Understanding gene regulatory networks has become one of the central research problems in bioinformatics. More than thirty algorithms have been proposed to identify DNA regulatory sites during the past thirty years. However, the prediction accuracy of these algorithms is still quite low. Ensemble algorithms have emerged as an effective strategy in bioinformatics for improving the prediction accuracy by exploiting the synergetic prediction capability of multiple algorithms. Results: We proposed a novel clustering-based ensemble algorithm named EMD for de novo motif discovery by combining multiple predictions from multiple runs of one or more base component algorithms. The ensemble approach is applied to the motif discovery problem for the first time. The algorithm is tested on a benchmark dataset generated from E. coli RegulonDB. The EMD algorithm has achieved 22.4% improvement in terms of the nucleotide level prediction accuracy over the best stand-alone component algorithm. The advantage of the EMD algorithm is more significant for shorter input sequences, but most importantly, it always outperforms or at least stays at the same performance level of the stand-alone component algorithms even for longer sequences. Conclusion: We proposed an ensemble approach for the motif discovery problem by taking advantage of the availability of a large number of motif discovery programs. We have shown that the ensemble approach is an effective strategy for improving both sensitivity and specificity, thus the accuracy of the prediction. The advantage of the EMD algorithm is its flexibility in the sense that a new powerful algorithm can be easily added to the system.