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

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Lamb ML,Jorgensen WL

doi

10.1021/jm980062o

subject

Has Abstract

pub_date

1998-10-08 00:00:00

pages

3928-39

issue

21

eissn

0022-2623

issn

1520-4804

pii

jm980062o

journal_volume

41

pub_type

杂志文章

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