CONFORMATIONAL STUDIES OF HUMAN ISLET AMYLOID PEPTIDE USING MOLECULAR-DYNAMICS AND SIMULATED ANNEALING METHODS

Molecular dynamics simulations and simulated annealing in vacuum, mode l aqueous solution, and simulated membrane were used to analyze the co nformational preferences of a segment spanning 20-29 residues of human islet amyloid polypeptide, [referred to as IAPP(H)(20-29)]. Molecular dynamics simulations were conducted at 300 K on IAPP(H)(20-29). The m inimum energy conformers obtained in model aqueous solution and vacuum exhibited similar structures. Even in the absence of any constraints on peptide bonds, trans conformation was preferred consistently by all the peptide bonds. Analysis of the minimum energy conformers indicate d that IAPP(H)(20-29) showed a strong preference for turn structures i n all the environments. These turn structures were stabilized by the f ormation of hydrogen bonds between the backbone amide and carbonyl gro ups. A good agreement was found between the results obtained from the molecular dynamics simulation and solid-state nmr experimental studies . (C) 1998 John Wiley & Sons, Inc.