Computational analysis of two similar neuropeptides yields distinct conformational ensembles

• Published in: Proteins, structure, function, and bioinformatics structure, function, and bioinformatics, 2000-08, Vol.40 (3), p.367-377
• Main Authors: Carlacci, Louis, Edison, Arthur S.
• Format: Article
• Language: English
• Subjects: Computer Simulation; configuration entropy; conformational search; conformer; FMRFamide - analogs & derivatives; Models, Molecular; Models, Theoretical; Molecular Conformation; Neuropeptides - chemistry; Nuclear Magnetic Resonance, Biomolecular; Oligopeptides - chemistry; peptide; solvation free energy; Thermodynamics
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/1097-0134(20000815)40:3<367::AID-PROT30>3.0.CO;2-C

Conformational states and thermodynamic properties for two similar neuropeptides, GDPFLRF‐NH2 and GYPFLRF‐NH2, have been computed by Monte Carlo simulated annealing (MCSA) conformational searches and Metropolis Monte Carlo (MMC) calculations. These peptides were recently shown to have dramatically different conformations in solution by NMR [Edison et al., J Neuroscience 1999;19:6318–6326]. Final conformations of multiple independent MCSA runs were the starting points for MMC calculations, and conformations saved at intervals during MMC runs were characterized in terms of total energy, configuration entropy, side‐chain fraction population, and ensemble average inter‐nuclear distances. Without the use of any NMR data‐generated pseudo‐potentials, the present calculations were in excellent qualitative agreement with all previous NMR experimental data and provided a foundation by which to more quantitatively interpret the experimental NMR results. Proteins 2000;40:367–377. © 2000 Wiley‐Liss, Inc.