Linked Life Data

21488062

Source:http://linkedlifedata.com/resource/pubmed/id/21488062

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2011-4-26
pubmed:abstractText
An understanding at the atomic level of the driving forces of inhibitor binding to the protein plasmepsin (PM) II would be of interest to the development of drugs against malaria. To this end, three state of the art computational techniques to compute relative free energies-thermodynamic integration (TI), Hamiltonian replica-exchange (H-RE) TI, and comparison of bound versus unbound ligand energy and entropy-were applied to a protein-ligand system of PM II and several exo-3-amino-7-azabicyclo[2.2.1]heptanes and the resulting relative free energies were compared with values derived from experimental IC(50) values. For this large and flexible protein-ligand system, the simulations could not properly sample the relevant parts of the conformational space of the bound ligand, resulting in failure to reproduce the experimental data. Yet, the use of Hamiltonian replica exchange in conjunction with thermodynamic integration resulted in enhanced convergence and computational efficiency compared to standard thermodynamic integration calculations. The more approximate method of calculating only energetic and entropic contributions of the ligand in its bound and unbound states from conventional molecular dynamics (MD) simulations reproduced the major trends in the experimental binding free energies, which could be rationalized in terms of energetic and entropic characteristics of the different structural and physico-chemical properties of the protein and ligands.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1096-987X
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Wiley Periodicals, Inc.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1801-12
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Calculation of binding free energies of inhibitors to plasmepsin II.
pubmed:affiliation
Department of Chemistry and Applied Biosciences, Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Zürich, ETH Zürich, CH-8093 Zürich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't