Conformational flexibility, internal hydrogen bonding, and passive membrane permeability: successful in silico prediction of the relative permeabilities of cyclic peptides.

Conformational flexibility, internal hydrogen bonding, and passive membrane permeability: successful in silico prediction of the relative permeabilities of cyclic peptides. Research Abstract Details 

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Conformational flexibility, internal hydrogen bonding, and passive membrane permeability: successful in silico prediction of the relative permeabilities of cyclic peptides. Abstract Text:

Taha Rezai,Jonathan E Bock,Mai V Zhou,Chakrapani Kalyanaraman,R Scott Lokey,Matthew P Jacobson,

We report an atomistic physical model for the passive membrane permeability of cyclic peptides. The computational modeling was performed in advance of the experiments and did not involve the use of "training data". The model explicitly treats the conformational flexibility of the peptides by extensive conformational sampling in low (membrane) and high (water) dielectric environments. The passive membrane permeabilities of 11 cyclic peptides were obtained experimentally using a parallel artificial membrane permeability assay (PAMPA) and showed a linear correlation with the computational results with R(2) = 0.96. In general, the results support the hypothesis, already well established in the literature, that the ability to form internal hydrogen bonds is critical for passive membrane permeability and can be the distinguishing factor among closely related compounds, such as those studied here. However, we have found that the number of internal hydrogen bonds that can form in the membrane and the solvent-exposed polar surface area correlate more poorly with PAMPA permeability than our model, which quantitatively estimates the solvation free energy losses upon moving from high-dielectric water to the low-dielectric interior of a membrane.

Conformational flexibility, internal hydrogen bonding, and passive membrane permeability: successful in silico prediction of the relative permeabilities of cyclic peptides. Publishing Authors By Initials

T Rezai,JE Bock,MV Zhou,C Kalyanaraman,RS Lokey,MP Jacobson,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation research

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Conformational flexibility, internal hydrogen bonding, and passive membrane permeability: successful in silico prediction of the relative permeabilities of cyclic peptides. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of the American Chemical Society

VOLUME: 128

Page Numbers: 14073-80

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 1

MONTH: Nov

YEAR: 2006

Conformational flexibility, internal hydrogen bonding, and passive membrane permeability: successful in silico prediction of the relative permeabilities of cyclic peptides. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503056

Conformational flexibility, internal hydrogen bonding, and passive membrane permeability: successful in silico prediction of the relative permeabilities of cyclic peptides. Keywords Mesh Terms:

KEYWORDS: Protein Conformation

MESH TERMS: chemistry

Chemical & Substance for Abstract: Conformational flexibility, internal hydrogen bonding, and passive membrane permeability: successful in silico prediction of the relative permeabilities of cyclic peptides. Information

Substance Name: Peptides, Cyclic

Registry Number: 0

Grant and Affiliation Information for Conformational flexibility, internal hydrogen bonding, and passive membrane permeability: successful in silico prediction of the relative permeabilities of cyclic peptides.

AFFILIATION: Department of Chemistry and Biochemistry, University of California at Santa Cruz, Santa Cruz, CA 95064, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM 56531

ACRONYM: GM

MEDLINETA: J Am Chem Soc

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