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

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.

Fitting Multimeric Protein Complexes into Electron Microscopy Maps Using 3D Zernike Descriptors

“…The 3DZDs of the EM maps were computed for an isosurface using a density range from 5 to 8 for the EM map at 10 Å resolution, while 7 to 11 for the case of the 15 Å resolution. These density ranges were shown to be effective in capturing characteristic shape features of EM maps in our previous study 45 .…”

Computational methods for constructing protein structure models from 3D electron microscopy maps

“…It was shown that the 3DZD is versatile and efficient for representing shapes of biomolecules, proteins, protein complexes, and small chemical ligand molecules, as well as EM maps (Kihara et al, 2011). In our work, we showed that the isosurface representation by 3DZD can distinguish EM maps of protein structures of the same fold even at 15 Å resolution (Sael and Kihara, 2010). A similar work has been performed that uses 3DZD for describing EM maps (Yin and Dokholyan, 2011).…”

“…Our group has shown that the 3D Zernike descriptors (3DZD), a mathematical series expansion of a 3D function, is effective for fast comparison of isosurfaces derived from EM density maps (Sael and Kihara, 2010). 3DZD represents a 3D object (isosurface of an EM density map) compactly as a vector of coefficient values of the series expansion in a rotationally invariant fashion.…”

Protein 3D Structure and Electron Microscopy Map Retrieval Using 3D‐SURFER2.0 and EM‐SURFER

“…In general, if the purpose is to find structures with the same fold classification as CATH (Sillitoe et al, 2015; see UNIT 1.28) or SCOP (Andreeva et al, 2008; see UNIT 1.26), the main chain atom representation performs best as long as the query molecule has a globular shape; the all-atom representation performs best if a query has a long tail or unstructured loop region. For the benchmark studies, see our previous work (Sael & Kihara, 2010). …”