title: PF2fit: Polar Fast Fourier Matched Alignment of Atomistic Structures with 3D Electron Microscopy Maps.
abstract: There continue to be increasing occurrences of both atomistic structure models in the PDB (possibly reconstructed from X-ray diffraction or NMR data), and 3D reconstructed cryo-electron microscopy (3D EM) maps (albeit at coarser resolution) of the same or homologous molecule or molecular assembly, deposited in the EMDB. To obtain the best possible structural model of the molecule at the best achievable resolution, and without any missing gaps, one typically aligns (match and fits) the atomistic structure model with the 3D EM map. We discuss a new algorithm and generalized framework, named PF(2) fit (Polar Fast Fourier Fitting) for the best possible structural alignment of atomistic structures with 3D EM. While PF(2) fit enables only a rigid, six dimensional (6D) alignment method, it augments prior work on 6D X-ray structure and 3D EM alignment in multiple ways: Scoring. PF(2) fit includes a new scoring scheme that, in addition to rewarding overlaps between the volumes occupied by the atomistic structure and 3D EM map, rewards overlaps between the volumes complementary to them. We quantitatively demonstrate how this new complementary scoring scheme improves upon existing approaches. PF(2) fit also includes two scoring functions, the non-uniform exterior penalty and the skeleton-secondary structure score, and implements the scattering potential score as an alternative to traditional Gaussian blurring. Search. PF(2) fit utilizes a fast polar Fourier search scheme, whose main advantage is the ability to search over uniformly and adaptively sampled subsets of the space of rigid-body motions. PF(2) fit also implements a new reranking search and scoring methodology that considerably improves alignment metrics in results obtained from the initial search.
authors.affiliation: Radhakrishna Bettadapura Computational Visualization Center/Department of Mechanical Engineering, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Radhakrishna
authors.initials: R
authors.lastname: Bettadapura
authors.affiliation: Muhibur Rasheed Computational Visualization Center/Department of Mechanical Engineering, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Muhibur
authors.initials: M
authors.lastname: Rasheed
authors.affiliation: Antje Vollrath Institut Computational Mathematics, Technische Universität Braunschweig, Braunschweig, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Vollrath
authors.affiliation: Chandrajit Bajaj Computational Visualization Center/Institute of Computational Engineering & Sciences/Department of Computer Science, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Chandrajit
authors.initials: C
authors.lastname: Bajaj
mesh_terms: D000465:Algorithms; D003461:Crystallography / Q000379:methods*; D005583:Fourier Analysis; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008854:Microscopy, Electron / Q000379:methods*; D011381:Programming Languages; D011487:Protein Conformation; D011506:Proteins / Q000648:ultrastructure*; D012984:Software; D013382:Subtraction Technique
chemical_list: D011506:Proteins