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Modeling protein loops using a ϕ i +1, Ψ i dimer database
Author(s) -
Sudarsanam Sucha,
Dubose Robert F.,
March Carl J.,
Srinivasan Subhashini
Publication year - 1995
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560040715
Subject(s) - protein data bank (rcsb pdb) , dihedral angle , protein data bank , dimer , peptide bond , crystallography , loop (graph theory) , loop modeling , chemistry , protein structure , bond length , stereochemistry , amino acid , protein structure prediction , mathematics , combinatorics , hydrogen bond , crystal structure , molecule , biochemistry , organic chemistry
We present an automated method for modeling backbones of protein loops. The method samples a database of ϕ i+1 and Ψ i angles constructed from a nonredundant version of the Protein Data Bank (PDB). The dihedral angles ϕ i+1 and Ψ i completely define the backbone conformation of a dimer when standard bond lengths, bond angles, and a trans planar peptide configuration are used. For the 400 possible dimers resulting from 20 natural amino acids, a list of allowed ϕ i+1 , Ψ i pairs for each dimer is created by pooling all such pairs from the loop segments of each protein in the nonredundant version of the PDB. Starting from the N‐terminus of the loop sequence, conformations are generated by assigning randomly selected pairs of ϕ i+1 , Ψ i for each dimer from the respective pool using standard bond lengths, bond angles, and a trans peptide configuration. We use this database to simulate protein loops of lengths varying from 5 to 11 amino acids in five proteins of known three‐dimensional structures. Typically, 10,000–50,000 models are simulated for each protein loop and are evaluated for stereochemical consistency. Depending on the length and sequence of a given loop, 50–80% of the models generated have no stereochemical strain in the backbone atoms. We demonstrate that, when simulated loops are extended to include flanking residues from homologous segments, only very few loops from an ensemble of sterically allowed conformations orient the flanking segments consistent with the protein topology. The presence of near‐native backbone conformations for loops from five different proteins suggests the completeness of the dimeric database for use in modeling loops of homologous proteins. Here, we take advantage of this observation to design a method that filters near‐native loop conformations from an ensemble of sterically allowed conformations. We demonstrate that our method eliminates the need for a loop‐closure algorithm and hence allows for the use of topological constraints of the homologous proteins or disulfide constraints to filter near‐native loop conformations.