Linked Life Data

14705028

Source:http://linkedlifedata.com/resource/pubmed/id/14705028

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-1-5
pubmed:abstractText
We have performed molecular dynamics (MD) simulations to study the dimerization, folding, and binding to a protein of peptides containing an unnatural amino acid. NMR studies have shown that the substitution of one residue in a tripeptide beta-strand by the unnatural amino acid Hao (5-HO2CCONH-2-MeO-C6H3-CO-NHNH2) modifies the conformational flexibility of the beta-strand and the hydrogen-bonding properties of its two edges: The number of hydrogen-bond donors and acceptors increases at one edge, whereas at the other, they are sterically hindered. In simulations in chloroform, the Hao-containing peptide 9 (i-PrCO-Phe-Hao-Val-NHBu) forms a beta-sheet-like hydrogen-bonded dimer, in good agreement with the available experimental data. Addition of methanol to the solution induces instability of this beta-sheet, as confirmed by the experiments. MD simulations also reproduce the folding of the synthetic peptide 1a (i-PrCO-Hao-Ut-Phe-Ile-Leu-NHMe) into a beta-hairpin-like structure in chloroform. Finally, the Hao-containing peptide, Ac-Ala-Hao-Ala-NHMe, is shown to form a stable complex with the Ras analogue, Rap1 A, in water at room temperature. Together with the available experimental data, these simulation studies indicate that Hao-containing peptides may serve as inhibitors of beta-sheet interactions between proteins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1097-0134
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
116-27
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Molecular dynamics simulations of peptides containing an unnatural amino acid: dimerization, folding, and protein binding.
pubmed:affiliation
Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Zurich, ETH Hönggerberg, 8093 Zürich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't