Molecular dynamics simulations and MM/GBSA methods to investigate binding mechanisms of aminomethylpyrimidine inhibitors with DPP-IV.

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Desheng L, Jian G, Yuanhua C, Wei C, Huai Z, Mingjuan J

Molecular dynamics simulations and MM/GBSA methods to investigate binding mechanisms of aminomethylpyrimidine inhibitors with DPP-IV.

Bioorg Med Chem Lett. 2011 Nov 15;21(22):6630-5. doi: 10.1016/j.bmcl.2011.09.093. Epub 2011 Sep 29.

PubMed ID

21996517 [ View in PubMed

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Abstract

The aminomethylpyrimidines were investigated as a novel class of DPP-IV inhibitors. In this Letter, the binding mechanisms of how slight change of substitution or position influences the binding affinity of five representative analogs was investigated by molecular dynamics simulation, free energy calculations and energy decomposition analysis. The conserved hydrogen bonds with Glu205 and Glu206 slightly favor the inhibitor binding; the van der Waals interactions, especially the two key contacts with Tyr547 and Tyr666, dominate in the binding free energy and play a crucial role on distinguishing the high active inhibitors from the low ones.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
5-(Aminomethyl)-6-(2,4-Dichlorophenyl)-2-(3,5-Dimethoxyphenyl)Pyrimidin-4-Amine	Dipeptidyl peptidase 4	IC 50 (nM)	0.1	N/A	N/A	Details