title: Protein Structure Determination by Assembling Super-Secondary Structure Motifs Using Pseudocontact Shifts.
abstract: Computational and nuclear magnetic resonance hybrid approaches provide efficient tools for 3D structure determination of small proteins, but currently available algorithms struggle to perform with larger proteins. Here we demonstrate a new computational algorithm that assembles the 3D structure of a protein from its constituent super-secondary structural motifs (Smotifs) with the help of pseudocontact shift (PCS) restraints for backbone amide protons, where the PCSs are produced from different metal centers. The algorithm, DINGO-PCS (3D assembly of Individual Smotifs to Near-native Geometry as Orchestrated by PCSs), employs the PCSs to recognize, orient, and assemble the constituent Smotifs of the target protein without any other experimental data or computational force fields. Using a universal Smotif database, the DINGO-PCS algorithm exhaustively enumerates any given Smotif. We benchmarked the program against ten different protein targets ranging from 100 to 220 residues with different topologies. For nine of these targets, the method was able to identify near-native Smotifs.
authors.affiliation: Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia; Department of Chemistry, University of Calgary, Calgary, AB T2N 1N4, Canada.
authors.forename: Kala Bharath
authors.initials: KB
authors.lastname: Pilla
authors.affiliation: Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Otting
authors.affiliation: Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia. Electronic address: t.huber@anu.edu.au.
authors.forename: Thomas
authors.initials: T
authors.lastname: Huber
mesh_terms: D000465:Algorithms; D007811:Lanthanum / Q000378:metabolism*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011506:Proteins; D007811:Lanthanum
keywords: 3D structure determination; DINGO-PCS; Pseudocontact shifts; Smotifs