Linked Life Data

10329153

Source:http://linkedlifedata.com/resource/pubmed/id/10329153

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-6-11
pubmed:abstractText
Titin, an important constituent of vertebrate muscles, is a protein of the order of a micrometer in length in the folded state. Atomic force microscopy and laser tweezer experiments have been used to stretch titin molecules to more than ten times their folded lengths. To explain the observed relation between force and extension, it has been suggested that the immunoglobulin and fibronectin domains unfold one at a time in an all-or-none fashion. We use molecular dynamics simulations to study the forced unfolding of two different fibronectin type 3 domains (the ninth, 9Fn3, and the tenth, 10Fn3, from human fibronectin) and of their heterodimer of known structure. An external biasing potential on the N to C distance is employed and the protein is treated in the polar hydrogen representation with an implicit solvation model. The latter provides an adiabatic solvent response, which is important for the nanosecond unfolding simulation method used here. A series of simulations is performed for each system to obtain meaningful results. The two different fibronectin domains are shown to unfold in the same way along two possible pathways. These involve the partial separation of the "beta-sandwich", an essential structural element, and the unfolding of the individual sheets in a stepwise fashion. The biasing potential results are confirmed by constant force unfolding simulations. For the two connected domains, there is complete unfolding of one domain (9Fn3) before major unfolding of the second domain (10Fn3). Comparison of different models for the potential energy function demonstrates that the dominant cohesive element in both proteins is due to the attractive van der Waals interactions; electrostatic interactions play a structural role but appear to make only a small contribution to the stabilization of the domains, in agreement with other studies of beta-sheet stability. The unfolding forces found in the simulations are of the order of those observed experimentally, even though the speed of the former is more than six orders of magnitude greater than that used in the latter.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-2836
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
288
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
441-59
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Forced unfolding of fibronectin type 3 modules: an analysis by biased molecular dynamics simulations.
pubmed:affiliation
Institut Le Bel, Université Louis Pasteur, 4 rue Blaise Pascal, Strasbourg, 67000, France.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't