Novel Methods for Rapid Comparison and Multimeric Protein Complex Fitting for Low-Resolution Electron Microscopy Data

Abstract

Recent advancements of experimental techniques for determining protein tertiary structures raise significant challenges for protein bioinformatics. Previously, we have introduced a method for protein surface shape representation using the 3D Zernike descriptors (3DZDs). The 3DZD enables fast structure database searches, taking advantage of its rotation invariance and compact representation. The 3DZD has been successfully applied for global protein surface shape comparison, local pocket shape comparison, protein docking prediction, and rapid small ligand molecule search. Here, we apply the 3DZD for comparing low-resolution structure data from the electron microscopy (EM). Two applications are presented. First, we use the 3DZD for rapid comparison for an EM density map of a protein structure to a database of EM data. We examined EM maps of varying resolutions and found that the method has good performance in identifying the structures of the same fold even for EM maps at a resolution of 15 Angstroms (Sael, Kihara , BMC Bioinformatics, in press). Next, we applied the 3DZD for fitting multiple component proteins into an EM map. The method integrates a multiple protein docking procedure and the 3DZD, which compares surface shape of docking conformation to the EM map. The multiple docking is performed by the Multi-LZerD algorithm, which starts by computing pairwise docking prediction of component chains by using the LZerD docking program, which our group have developed recently (Venkatraman et al., BMC Bioinformatics, 2010). Multi-LZerD combines the pairwise docking results generating a couple of hundreds solutions. Then the fitness of the multiple docking decoys and the EM map is quantified by using the 3DZD. Overall, we show that the 3DZD is powerful in comparing low-resolution structure data for comparison and multiple-docking guided by the low-resolution data.