title: The AUDANA algorithm for automated protein 3D structure determination from NMR NOE data.
abstract: We introduce AUDANA (Automated Database-Assisted NOE Assignment), an algorithm for determining three-dimensional structures of proteins from NMR data that automates the assignment of 3D-NOE spectra, generates distance constraints, and conducts iterative high temperature molecular dynamics and simulated annealing. The protein sequence, chemical shift assignments, and NOE spectra are the only required inputs. Distance constraints generated automatically from ambiguously assigned NOE peaks are validated during the structure calculation against information from an enlarged version of the freely available PACSY database that incorporates information on protein structures deposited in the Protein Data Bank (PDB). This approach yields robust sets of distance constraints and 3D structures. We evaluated the performance of AUDANA with input data for 14 proteins ranging in size from 6 to 25 kDa that had 27-98 % sequence identity to proteins in the database. In all cases, the automatically calculated 3D structures passed stringent validation tests. Structures were determined with and without database support. In 9/14 cases, database support improved the agreement with manually determined structures in the PDB and in 11/14 cases, database support lowered the r.m.s.d. of the family of 20 structural models.
authors.affiliation: National Magnetic Resonance Facility at Madison and Biochemistry Department, University of Wisconsin-Madison, Madison, WI, 53706, USA. whlee@nmrfam.wisc.edu.
authors.forename: Woonghee
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Chad M
authors.initials: CM
authors.lastname: Petit
authors.affiliation: National Magnetic Resonance Facility at Madison and Biochemistry Department, University of Wisconsin-Madison, Madison, WI, 53706, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cornilescu
authors.affiliation: National Magnetic Resonance Facility at Madison and Biochemistry Department, University of Wisconsin-Madison, Madison, WI, 53706, USA.
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Stark
authors.affiliation: National Magnetic Resonance Facility at Madison and Biochemistry Department, University of Wisconsin-Madison, Madison, WI, 53706, USA. markley@nmrfam.wisc.edu.
authors.forename: John L
authors.initials: JL
authors.lastname: Markley
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012984:Software; D013329:Structure-Activity Relationship; D064878:Web Browser
chemical_list: D011506:Proteins
keywords: 3D structure determination; Automated structure calculation; NOE assignment; PACSY database; PONDEROSA; Sequence-structure correlation