Computational investigations of structural changes resulting from point mutations in a collagen‐like peptide

The results of 0.5–1.0 ns molecular dynamics simulations of the collagen‐like peptides [(POG) 4 (POA)(POG) 4 ] 3 and [(POG) 9 ] 3 (POG: proline–hydroxyproline–glycine) are presented.* All simulations were performed using the AMBER‐94 molecular mechanical force field with a shell of TIP3P waters surrounding the peptides. The initial geometries for the collagen‐like peptides included an x‐ray crystallographic structure, a computer‐generated structure, a [(POG) 9 ] 3 structure modeled from the x‐ray structure, and the x‐ray structure with crystallographic waters replaced with a shell of modeled TIP3P waters. We examined the molecular dynamics peptide residue rms deviation fluctuations, dihedral angles, molecular and chain end‐to‐end distances, helical parameters, and peptide–peptide and peptide–solvent hydrogen‐bonding patterns. Our molecular dynamics simulations of [(POG) 4 (POA)(POG) 4 ] 3 show average structures and internal coordinates similar to the x‐ray crystallographic structure. Our results demonstrate that molecular dynamics can be used to reproduce the experimental structures of collagen‐like peptides. We have demonstrated the feasibility of using the AMBER‐94 molecular mechanical force field, which was parameterized to model nucleic acids and globular proteins, for fibril proteins. We provide a new interpretation of peptide–solvent hydrogen bonding and a peptide–peptide hydrogen bonding pattern not previously reported in x‐ray studies. Last, we report on the differences, in particular with respect to main‐chain dihedral angles and hydrogen bonding, between the native and mutant collagen‐like peptides. © 1999 John Wiley & Sons, Inc. Biopoly 49: 167–183, 1999