Investigations of neurotrophic inhibitors of FK506 binding protein via Monte Carlo simulations.

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Lamb ML, Jorgensen WL

Investigations of neurotrophic inhibitors of FK506 binding protein via Monte Carlo simulations.

J Med Chem. 1998 Oct 8;41(21):3928-39.

PubMed ID

9767630 [ View in PubMed

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Abstract

The binding and solution-phase properties of six inhibitors of FK506 binding protein (FKBP12) were investigated using free energy perturbation techniques in Monte Carlo statistical mechanics simulations. These nonimmunosuppressive molecules are of current interest for their neurotrophic activity when bound to FKBP12 as well as for their potential as building blocks for chemical inducers of protein dimerization. Relative binding affinities were computed and analyzed for ligands differing by a phenyl ring, an external phenyl or pyridyl substituent, and a pipecolyl or prolyl ring. Such results are, in general, valuable for inhibitor optimization and, in the present case, bring into question some of the previously reported binding data.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Gpi-1046	Peptidyl-prolyl cis-trans isomerase FKBP1A	Ki (nM)	7.5	N/A	N/A	Details