Conformational studies of human islet amyloid peptide using molecular dynamics and simulated annealing methods.
Molecular dynamics simulations and simulated annealing in vacuum, model aqueous solution, and simulated membrane were used to analyze the conformational preferences of a segment spanning 20-29 residues of human islet amyloid polypeptide, [referred to as IAPPH (20-29)]. Molecular dynamics simulations were conducted at 300 K on IAPPH (20-29). The minimum 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 indicated that IAPPH (20-29) showed a strong preference for turn structures in all the environments. These turn structures were stabilized by the formation of hydrogen bonds between the backbone amide and carbonyl groups. A good agreement was found between the results obtained from the molecular dynamics simulation and solid-state nmr experimental studies.
Ilangovan
U
U
Biophysics Research Division, University of Michigan, Ann Arbor 48109-1055, USA.
Ramamoorthy
A
A
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D006801:Humans; D007515:Islets of Langerhans / Q000737:chemistry*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013816:Thermodynamics
D000682:Amyloid