Linked Life Data

8786412

Source:http://linkedlifedata.com/resource/pubmed/id/8786412

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1996-9-20
pubmed:abstractText
VX-478 belongs to a novel class of HIV-1 protease inhibitors that are based on N,N-disubstituted benzene sulfonamides. Force field parameters for the N,N-dialkyl benzene sulfonamide moiety have been assembled from the literature and from our own ab initio calculations. These parameters were employed to calculate solvation and binding free energy differences between VX-478 and two analogs. The free energy perturbation method has been used to determine these differences using two approaches. In the first approach, intergroup interaction terms only were included in the calculation of free energies (as in most reports of free energy calculations using AMBER). In the second approach, both the inter- and intragroup interaction terms were included. The results obtained with the two approaches are in excellent agreement with each other and are also in close agreement with the experimental results. The solvation free energies of N,N-dimethyl benzene sulfonamide derivatives (truncated models of the inhibitors), calculated using continuum solvation (AMSOL) methods, are found to be in qualitative agreement with the experimental and free energy perturbation results. The binding and solvation free energy results are discussed in the context of structure-based drug design to show how physicochemical properties (for example aqueous solubilities and bioavailabilities) of these HIV-I protease inhibitors were improved, while maintaining their inhibitory potency.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0920-654X
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23-30
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Calculation of solvation and binding free energy differences between VX-478 and its analogs by free energy perturbation and AMSOL methods.
pubmed:affiliation
Vertex Pharmaceuticals Inc., Cambridge, MA 02139, USA.
pubmed:publicationType
Journal Article, Comparative Study