Improved protein surface comparison and application to low-resolution protein structure data

Lee Sael,Daisuke Kihara

doi:10.1186/1471-2105-11-s11-s2

Abstract

BackgroundRecent advancements of experimental techniques for determining protein tertiary structures raise significant challenges for protein bioinformatics. With the number of known structures of unknown function expanding at a rapid pace, an urgent task is to provide reliable clues to their biological function on a large scale. Conventional approaches for structure comparison are not suitable for a real-time database search due to their slow speed. Moreover, a new challenge has arisen from recent techniques such as electron microscopy (EM), which provide low-resolution structure data. 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 search results of protein surface represented with the 3DZD has showngood agreement with the existing structure classifications, but some discrepancies were also observed.ResultsThe three new surface representations of backbone atoms, originally devised all-atom-surface representation, and the combination of all-atom surface with the backbone representation are examined. All representations are encoded with the 3DZD. Also, we have investigated the applicability of the 3DZD for searching protein EM density maps of varying resolutions. The surface representations are evaluated on structure retrieval using two existing classifications, SCOP and the CE-based classification.ConclusionsOverall, the 3DZDs representing backbone atoms show better retrieval performance than the original all-atom surface representation. The performance further improved when the two representations are combined. Moreover, we observed that the 3DZD is also powerful in comparing low-resolution structures obtained by electron microscopy.

Highlights

Recent advancements of experimental techniques for determining protein tertiary structures raise significant challenges for protein bioinformatics
We demonstrate that the new mainchain surface representations encoded by the 3D Zernike descriptors (3DZDs) have a better agreement to CE and SCOP as compared to the original all-atom surface representation introduced in the previous study [16]
Observing the agreement between the electron microscopy (EM) isosurface and structures coded by the 3DZD, we investigate further if the 3DZD can be used for searching similar EM density maps of protein structures (Table 2)

Summary

Introduction

Recent advancements of experimental techniques for determining protein tertiary structures raise significant challenges for protein bioinformatics. Development of a new generation of structure analysis tools, which allow a fast screening of large structure databases and can handle low resolution structure data, is needed With this in mind, we represent protein structures as surface shapes by the 3D Zernike descriptors (3DZD) [13,14,15,16,17]. There have been previous works which employ a protein surface representation [15], such as volumetric representation [18], convex hull [19], and the spin image [20] Compared to those works, the 3DZD has the following properties that make it ideal for use in protein shape analyses. The 3DZD has been further applied for protein-protein docking prediction [21], local surface comparison [22], pocket shape matching for structure-based function prediction [23], and ligand molecule screening [13,24]

Methods

Results

Conclusion