Calculation of binding free energies for non-zinc chelating pyrimidine dicarboxamide inhibitors with MMP-13.

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Carrascal N, Rizzo RC

Calculation of binding free energies for non-zinc chelating pyrimidine dicarboxamide inhibitors with MMP-13.

Bioorg Med Chem Lett. 2009 Jan 1;19(1):47-50. doi: 10.1016/j.bmcl.2008.11.038. Epub 2008 Nov 18.

PubMed ID

19042129 [ View in PubMed

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Abstract

All-atom molecular dynamics (MD) simulations in both explicit and implicit solvent, followed by MM-GBSA energy analysis, have been used to estimate binding free energies of four pyrimidine dicarboxamide inhibitors with human collagenase-3 (MMP-13) for comparison with experimental activities. Energetic analysis reveals that affinity is driven primarily by favorable van der Waals interactions and burial of total surface area. The computed effects of desolvation, as a function of ligand structure, quantitatively show that hydrophilic derivatives pay greater penalties upon binding than their related more hydrophobic analogs.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
PYRIMIDINE-4,6-DICARBOXYLIC ACID BIS-(3-METHYL-BENZYLAMIDE)	Collagenase 3	IC 50 (nM)	72	N/A	N/A	Details
PYRIMIDINE-4,6-DICARBOXYLIC ACID BIS-(4-FLUORO-3-METHYL-BENZYLAMIDE)	Collagenase 3	IC 50 (nM)	8	N/A	N/A	Details
PYRIMIDINE-4,6-DICARBOXYLIC ACID BIS-[(PYRIDIN-3-YLMETHYL)-AMIDE]	Collagenase 3	IC 50 (nM)	6600	N/A	N/A	Details