Prediction of the permeability of neutral drugs inferred from their solvation properties

Edoardo Milanetti; Domenico Raimondo; Anna Tramontano

doi:10.1093/bioinformatics/btv725

Prediction of the permeability of neutral drugs inferred from their solvation properties

Edoardo Milanetti, Domenico Raimondo, Anna Tramontano

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Motivation: Determination of drug absorption is an important component of the drug discovery and development process in that it plays a key role in the decision to promote drug candidates to clinical trials. We have developed a method that, on the basis of an analysis of the dynamic distribution of water molecules around a compound obtained by molecular dynamics simulations, can compute a parameter-free value that correlates very well with the compound permeability measured using the human colon adenocarcinoma (Caco-2) cell line assay. Results: The method has been tested on twenty-three neutral drugs for which a consistent set of experimental data is available. We show here that our method reproduces the experimental data better than other existing tools. Furthermore it provides a detailed view of the relationship between the hydration and the permeability properties of molecules.

Original language	English (US)
Pages (from-to)	1163-1169
Number of pages	7
Journal	Bioinformatics
Volume	32
Issue number	8
DOIs	https://doi.org/10.1093/bioinformatics/btv725
State	Published - Dec 10 2015
Externally published	Yes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): KUK-I1-012-43
Acknowledgements: KAUST Award No. KUK-I1-012-43 made by King Abdullah University of Scienceand Technology. Progetto di Ricerca di Università, anno 2014 - prot.C26A14RFYP, EPIGEN flagship Project and PRIN 20108XYHJS
This publication acknowledges KAUST support, but has no KAUST affiliated authors.

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10.1093/bioinformatics/btv725

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title = "Prediction of the permeability of neutral drugs inferred from their solvation properties",

abstract = "Motivation: Determination of drug absorption is an important component of the drug discovery and development process in that it plays a key role in the decision to promote drug candidates to clinical trials. We have developed a method that, on the basis of an analysis of the dynamic distribution of water molecules around a compound obtained by molecular dynamics simulations, can compute a parameter-free value that correlates very well with the compound permeability measured using the human colon adenocarcinoma (Caco-2) cell line assay. Results: The method has been tested on twenty-three neutral drugs for which a consistent set of experimental data is available. We show here that our method reproduces the experimental data better than other existing tools. Furthermore it provides a detailed view of the relationship between the hydration and the permeability properties of molecules.",

author = "Edoardo Milanetti and Domenico Raimondo and Anna Tramontano",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): KUK-I1-012-43 Acknowledgements: KAUST Award No. KUK-I1-012-43 made by King Abdullah University of Scienceand Technology. Progetto di Ricerca di Universit{\`a}, anno 2014 - prot.C26A14RFYP, EPIGEN flagship Project and PRIN 20108XYHJS This publication acknowledges KAUST support, but has no KAUST affiliated authors.",

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doi = "10.1093/bioinformatics/btv725",

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AU - Milanetti, Edoardo

AU - Raimondo, Domenico

AU - Tramontano, Anna

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): KUK-I1-012-43 Acknowledgements: KAUST Award No. KUK-I1-012-43 made by King Abdullah University of Scienceand Technology. Progetto di Ricerca di Università, anno 2014 - prot.C26A14RFYP, EPIGEN flagship Project and PRIN 20108XYHJS This publication acknowledges KAUST support, but has no KAUST affiliated authors.

PY - 2015/12/10

Y1 - 2015/12/10

N2 - Motivation: Determination of drug absorption is an important component of the drug discovery and development process in that it plays a key role in the decision to promote drug candidates to clinical trials. We have developed a method that, on the basis of an analysis of the dynamic distribution of water molecules around a compound obtained by molecular dynamics simulations, can compute a parameter-free value that correlates very well with the compound permeability measured using the human colon adenocarcinoma (Caco-2) cell line assay. Results: The method has been tested on twenty-three neutral drugs for which a consistent set of experimental data is available. We show here that our method reproduces the experimental data better than other existing tools. Furthermore it provides a detailed view of the relationship between the hydration and the permeability properties of molecules.

AB - Motivation: Determination of drug absorption is an important component of the drug discovery and development process in that it plays a key role in the decision to promote drug candidates to clinical trials. We have developed a method that, on the basis of an analysis of the dynamic distribution of water molecules around a compound obtained by molecular dynamics simulations, can compute a parameter-free value that correlates very well with the compound permeability measured using the human colon adenocarcinoma (Caco-2) cell line assay. Results: The method has been tested on twenty-three neutral drugs for which a consistent set of experimental data is available. We show here that our method reproduces the experimental data better than other existing tools. Furthermore it provides a detailed view of the relationship between the hydration and the permeability properties of molecules.

UR - http://hdl.handle.net/10754/599385

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SP - 1163

EP - 1169

JO - Bioinformatics

JF - Bioinformatics

IS - 8

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Prediction of the permeability of neutral drugs inferred from their solvation properties

Abstract

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