Abstract

Novel computational methods for multiple protein docking and for fitting high-resolution structures of multiple proteins into a cryoelectron microscopy map are presented (2 papers). The method named EMLZerD generates a pool of candidate multiple protein docking conformations of component proteins using a novel multiple protein docking method, Multi-LZerD, which are later compared with a provided electron microscopy (EM) density map to select the ones that fit well into the EM map (Esquivel-Rodriguez & Kihara, J. Phys Chem B, 2012). Multi-LZerD (Esquivel-Rodriguez et al., Proteins, 2012) builds models of multimeric complexes by effectively reusing pairwise docking predictions of component proteins. A genetic algorithm is applied to explore the conformational space followed by a structure refinement procedure. 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 root-mean-square deviation of less than 2.5 Å were obtained for 14 cases while medium range resolution structures with correct topology were computed for the additional 5 cases.