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Stereoselectivity by enantiomeric inhibitors of matrix metalloproteinase-8: new insights from molecular dynamics simulations
- Source :
- Journal of medicinal chemistry 50 (2007): 211–218. doi:10.1021/jm0608457, info:cnr-pdr/source/autori:Aschi M., Besker N., Re N., Pochetti G., Coletti C., Gallina C., Mazza F./titolo:Stereoselectivity by enantiomeric inhibitors of matrix metalloproteinase-8: new insights from molecular dynamics simulations/doi:10.1021%2Fjm0608457/rivista:Journal of medicinal chemistry/anno:2007/pagina_da:211/pagina_a:218/intervallo_pagine:211–218/volume:50
- Publication Year :
- 2007
- Publisher :
- American Chemical Society, [Easton, Pa.] , Stati Uniti d'America, 2007.
-
Abstract
- Molecular Dynamics simulations in aqueous solution were performed for the matrix metalloproteinase-8 (MMP-8) free catalytic domain and for its complexes with the (R)- and (S)-[1-(4‘-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl] phosphonate. The 144−155 loop of the enzyme undergoes a drastic decrease of mobility once complexed with both enantiomers. The two enantiomers induce a different decrease of conformational entropy upon complexation. The higher affinity of the R-enantiomer can be related to the lower loss of conformational entropy accompanying its binding. The differences in the dynamical behavior of the protein induced by the two enantiomers are discussed at molecular level and the mode of binding of the simulated complexes is compared with that previously determined by X-ray crystallography.
- Subjects :
- Models, Molecular
Stereochemistry
Entropy
Molecular Conformation
Organophosphonates
Quantitative Structure-Activity Relationship
Stereoisomerism
Matrix Metalloproteinase Inhibitors
chemistry.chemical_compound
Molecular dynamics
Catalytic Domain
Drug Discovery
Protease Inhibitors
Sulfonamides
Biphenyl Compounds
Conformational entropy
Phosphonate
Biphenyl compound
Matrix Metalloproteinase 8
chemistry
Molecular Medicine
Stereoselectivity
Enantiomer
Entropy (order and disorder)
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Journal of medicinal chemistry 50 (2007): 211–218. doi:10.1021/jm0608457, info:cnr-pdr/source/autori:Aschi M., Besker N., Re N., Pochetti G., Coletti C., Gallina C., Mazza F./titolo:Stereoselectivity by enantiomeric inhibitors of matrix metalloproteinase-8: new insights from molecular dynamics simulations/doi:10.1021%2Fjm0608457/rivista:Journal of medicinal chemistry/anno:2007/pagina_da:211/pagina_a:218/intervallo_pagine:211–218/volume:50
- Accession number :
- edsair.doi.dedup.....0fce85dde2847ffea7afe20c5d0e8552