Recognition in cell adhesion. A comparative study of the conformations of RGD-containing peptides by Monte Carlo and NMR methods.
Many of the proteins that mediate cell adhesion processes processes-fibronectin, fibrinogen, vitronectin, von Willebrand factor, osteopontin, laminin and various collagens--contain the amino acid sequence Arg-Gly-Asp. Short peptides that include this sequence have been shown to inhibit the interactions of cell adhesion proteins with their receptors and to have dramatic effects on developmental processes involving cellular recognition. In order to determine which conformations are accessible to Arg-Gly-Asp containing peptides, we analyzed tri-, tetra- and pentapeptides using molecular mechanics and Monte Carlo methods, and studied the solution conformations of the pentapeptide Gly-Arg-Gly-Asp-Ser using nuclear magnetic resonance techniques. The Monte Carlo method was used to: (a) identify the low energy conformations of the peptides and (b) evaluate their thermodynamic properties. In the case of the pentapeptide Gly-Arg-Gly-Asp-Gly, the four stable conformations include three with reverse turns and one open structure. The conformations found in this analysis are compatible with the nuclear magnetic resonance (nuclear Overhauser effect) data.
Cachau
R E
RE
Johns Hopkins University School of Medicine, Department of Biophysics, Baltimore, Maryland 21205.
Serpersu
E H
EH
Mildvan
A S
AS
August
J T
JT
Amzel
L M
LM
D000595:Amino Acid Sequence; D015815:Cell Adhesion Molecules; D055598:Chemical Phenomena; D002621:Chemistry; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D009842:Oligopeptides; D011487:Protein Conformation; D013816:Thermodynamics
D015815:Cell Adhesion Molecules; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid