New Theoretical Methodology for Elucidating the Solution Structure of Peptides from NMR Data. 3. Solvation Effects

A short linear peptide in solution may populate several stable states (denoted here microstates) in thermodynamic equilibrium. Elucidating its dynamic 3D structure by multidimensional nuclear magnetic resonance (NMR) is complex, since the experimentally measured nuclear Overhauser effect intensities (NOEs) represent averages over the individual contributions. In previous papers (paper 1, Meirovitch, H.; et al. J. Phys. Chem. 1995, 99, 4847; and paper 2, Meirovitch, E.; Meirovitch, H. Biopolymers 1996, 38, 69) we have developed a new theoretical methodology based on statistical mechanical considerations for analyzing NMR data from flexible molecules and applied it to Leu-enkephalin (H-Tyr-Gly-Gly-Phe-Leu-OH) using the potential energy function ECEPP. The corresponding experimental NOEs have been obtained from a cryoprotective solution of this molecule. Our approach is based on a conformational search which identifies a set of significantly different low-energy structures within a certain energy range above...