Open AccessIntroduction of short-range restrictions in a protein-folding algorithm involving a long-range geometrical restriction and short-, medium-, and long-range interactions
Author(s) -
Hagai Meirovitch,
H. A. Scheraga
Publication year - 1981
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.78.11.6584
Subject(s) - range (aeronautics) , energy minimization , crystallography , energy (signal processing) , protein structure prediction , folding (dsp implementation) , algorithm , protein folding , chemistry , protein structure , physics , mathematics , geometry , computational chemistry , materials science , nuclear magnetic resonance , quantum mechanics , electrical engineering , composite material , engineering
A protein-folding algorithm, based on short-range and geometrical long-range restrictions, is applied to bovine pancreatic trypsin inhibitor (BPTI). These restrictions are used to define a starting conformation, SI, by means of a space-filling model of the protein, whose energy is then minimized. The long-range restriction is the imposition of the native spatial geometric arrangement of the loops (SGAL) formed by the disulfide bonds. The short-range restrictions are applied as follows: the (ϕ, ψ) map of each residue is divided into six regions (corresponding to the right- and left-handed α-helical, extended, right- and left-handed bridge, and coil states) and the individual residues are placed in the states of the native structure [althoughnot in conformations with the correct values of (ϕ, ψ)]. Minimization of the energy of SI leads to a structure, SF, with a root-mean-square deviation of 4.4 Å from NI, a previously energy-optimized version of the x-ray structure. SF is closer to the native structure than is the structure RF, which was obtained previously by imposing only the correct SGAL as a restriction. The energy of SF is much lower than that of RF but still larger than the energy of NF (the energy-refined x-ray structure).