Linked Life Data

19899169

Source:http://linkedlifedata.com/resource/pubmed/id/19899169

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-1-26
pubmed:abstractText
We present a novel multi-level methodology to explore and characterize the low energy landscape and the thermodynamics of proteins. Traditional conformational search methods typically explore only a small portion of the conformational space of proteins and are hard to apply to large proteins due to the large amount of calculations required. In our multi-scale approach, we first provide an initial characterization of the equilibrium state ensemble of a protein using an efficient computational conformational sampling method. We then enrich the obtained ensemble by performing short Molecular Dynamics (MD) simulations on selected conformations from the ensembles as starting points. To facilitate the analysis of the results, we project the resulting conformations on a low-dimensional landscape to efficiently focus on important interactions and examine low energy regions. This methodology provides a more extensive sampling of the low energy landscape than an MD simulation starting from a single crystal structure as it explores multiple trajectories of the protein. This enables us to obtain a broader view of the dynamics of proteins and it can help in understanding complex binding, improving docking results and more. In this work, we apply the methodology to provide an extensive characterization of the bound complexes of the C3d fragment of human Complement component C3 and one of its powerful bacterial inhibitors, the inhibitory domain of Staphylococcus aureus extra-cellular fibrinogen-binding domain (Efb-C) and two of its mutants. We characterize several important interactions along the binding interface and define low free energy regions in the three complexes. Proteins 2010. (c) 2009 Wiley-Liss, Inc.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-11125149, http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-14531054, http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-16200636, http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-16222654, http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-16389462, http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-16785435, http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-17158570, http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-17351618, http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-17813860, http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-18658214, http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-18721882, http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-18808094, http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-19017934, http://linkedlifedata.com/resource/pubmed/commentcorrection/19899169-8552589
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1097-0134
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
78
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1004-14
pubmed:dateRevised
2011-7-25
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Multi-scale characterization of the energy landscape of proteins with application to the C3D/Efb-C complex.
pubmed:affiliation
Department of Computer Science, Rice University, Houston, Texas 77005, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural