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Determination of the major solution conformation of tyrocidine A, using molecular mechanics energy minimization and NMR‐derived distance and torsion angle constraints
Author(s) -
Tonge Alan P.,
Murrayrust Peter,
Gibbons William A.,
McLachlan Lesley K.
Publication year - 1988
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.540090511
Subject(s) - conformational isomerism , dihedral angle , energy minimization , ramachandran plot , chemistry , torsion (gastropod) , antiparallel (mathematics) , side chain , molecular mechanics , crystallography , molecule , hydrogen bond , computational chemistry , molecular dynamics , protein structure , physics , quantum mechanics , medicine , biochemistry , magnetic field , polymer , surgery , organic chemistry
Molecular mechanics energy calculations coupled with nuclear magnetic resonance‐determined distance and torsion angle constraints have been used to determine the three‐dimensional structure of tyrocidine A, a cyclic decapeptide which exists largely as a single conformation in solution. Two open‐chain polyalanine models were used to represent separate halves of the peptide backbone and a combinatorial method of searching conformation space used to generate candidate structures consistent with experimental distance constraints. These structures were energy‐minimized using the AMBER molecular mechanics forcefield and the resulting conformations classified by factor analysis of their Cartesian coordinates. Representative low‐energy conformers of the two halves of the backbone were fused together and two candidate conformations of the completed backbone refined by further minimization using both distance and torsional constraints. Side chains were then added as their experimentally preferred rotamers and the whole molecule minimized without constraints to give the final model structure. This shows type II' and III ß turns at residues 4–5 and 9–10, respectively, coupled by twisted antiparallel strands which show hydrogen bonds between all four pairs of opposing peptide groups. The backbone conformation of residues 2–6 closely resembles that found in the crystal structure of gramicidin S.