Macromolecular Structure Modeling and Electron Microscopy Fitting using 3D Zernike Descriptors

Abstract

A novel computational method for fitting high-resolution structures of multiple proteins into a cryoelectron microscopy (EM) map is presented. The method named EMLZerD generates a pool of candidate complex conformations of component proteins using a novel multiple protein docking method, Multi-LZerD, which are later compared with a provided EM map to select the ones that fit well into the EM map (Esquivel-Rodriguez & Kihara, J. Phys Chem B, 2012). Multi-LZerD (Esquivel-Rodriguez & Kihara, Proteins, 2012) builds models of multimeric protein complexes by effectively reusing pairwise docking predictions of component proteins. The comparison of docking conformations and the EM map is performed using the 3D Zernike descriptor (3DZD), a mathematical series expansion of three-dimensional functions. The 3DZD provides a unified representation of the surface shape of multimeric protein complex models and EM maps, which allows a convenient, fast quantitative comparison of the three-dimensional structural data. Out of 19 multimeric complexes tested, near native complex structures with a RMSD of less than 2.5 A were obtained for 14 cases while medium range resolution structures with correct topology were computed for the additional 5 cases.View Large Image | View Hi-Res Image | Download PowerPoint Slide