Linked Life Data

17957770

Source:http://linkedlifedata.com/resource/pubmed/id/17957770

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-2-27
pubmed:abstractText
By docking flexible balanol to a rigid model of protein kinase A (PKA), we found that a new simulated annealing protocol termed disrupted velocity simulated annealing (DIVE-SA) outperformed the replica-exchange method and the traditional simulated annealing method in identifying the correct docking pose. In this protocol, the atomic velocities were reassigned periodically to encourage the system to sample a large conformational space. We also found that scaling potential energy surface to reduce structural transition barriers could further facilitate docking. The DIVE-SA method was then evaluated on its ability to perform flexible ligand-flexible protein docking of three ligands (balanol, a balanol analog, and ATP) to PKA. To reduce computational time and to avoid possible unphysical structural changes resulting from the use of nonoptimal force fields, a soft restrain was applied to keep the root-mean-square-deviation (RMSD) between instantaneous protein structures and a chosen reference structure small. Because the restrain was applied to the overall RMSD rather than to individual atoms, a protein could still experience relatively large conformational changes during docking. To examine the impact of applying such a restrain on docking, we constructed two semi-flexible protein models by choosing two different crystal structures as reference. Both the balanol analog and ATP were able to dock to either one of these semi-flexible protein models. On the other hand, balanol could only dock well to one of them. Further analysis indicated that the restrain on the glycine-rich loop was too strong, preventing it to adjust its structure to accommodate balanol in the binding pocket of PKA. Removing the restrain on the glycine-rich loop resulted in much better docking poses. This finding demonstrates the important role that the flexibility of the glycine-rich loop play in accepting different ligands and should profitably not be restrained in molecular docking so that more diverse ligands can be studied.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1097-0134
pubmed:author
pubmed:copyrightInfo
(c) 2007 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
440-54
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Flexible protein-flexible ligand docking with disrupted velocity simulated annealing.
pubmed:affiliation
Department of Chemistry and Biochemistry, University of Missouri-Saint Louis, One University Boulevard, St. Louis, Missouri 63121, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Evaluation Studies, Research Support, N.I.H., Extramural