title: A new approach to protein fold recognition based on Delaunay tessellation of protein structure.
abstract: We propose new algorithms for sequence-structure compatibility (fold recognition) searches in multi-dimensional sequence-structure space. Individual amino acid residues in protein structures are represented by their C alpha atoms; thus each protein is described as a collection of points in three-dimensional space. Delaunay tessellation of a protein generates an aggregate of space-filling, irregular tetrahedra, or Delaunay simplices. Statistical analysis of quadruplet residue compositions of all Delaunay simplices in a representative dataset of protein structures leads to a novel four body contact residue potential expressed as log likelihood factor q. The q factors are calculated for native 20 letter amino acid alphabet and several reduced alphabets. Two sequence-structure compatibility functions are computed as (i) the sum of q factors for all Delaunay simplices in a given protein, or (ii) 3D-1D Delaunay tessellation profiles where the individual residue profile value is calculated as the sum of q factors for all simplices that share this vertex residue. Both threading functions have been implemented in structure-recognizes-sequence and sequence-recognizes-structure protocols for protein fold recognition. We find that both profile and total score based threading functions can distinguish both the native fold from incorrect folds for a sequence, and the native sequence from non-native sequences for a fold.
authors.affiliation: Laboratory for Molecular Modeling, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zheng
authors.forename: S J
authors.initials: SJ
authors.lastname: Cho
authors.forename: I I
authors.initials: II
authors.lastname: Vaisman
authors.forename: A
authors.initials: A
authors.lastname: Tropsha
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D016208:Databases, Factual; D016013:Likelihood Functions; D008956:Models, Chemical; D008958:Models, Molecular; D009154:Mutation; D011381:Programming Languages; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011506:Proteins