Assessing the Accuracy and Performance of Implicit Solvent Models for Drug Molecules: Conformational Ensemble Approaches

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F13%3A10191809" target="_blank" >RIV/00216208:11310/13:10191809 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/13:00394160 RIV/61989592:15310/13:33148140

Výsledek na webu

<a href="http://pubs.acs.org/doi/abs/10.1021/jp402117c" target="_blank" >http://pubs.acs.org/doi/abs/10.1021/jp402117c</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jp402117c" target="_blank" >10.1021/jp402117c</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Assessing the Accuracy and Performance of Implicit Solvent Models for Drug Molecules: Conformational Ensemble Approaches

Popis výsledku v původním jazyce

The accuracy and performance of implicit solvent methods for solvation free energy calculations were assessed on a set of 20 neutral drug molecules. Molecular dynamics (MD) provided ensembles of conformations in water and water saturated octanol. The solvation free energies were calculated by popular implicit solvent models based on quantum mechanical (QM) electronic densities (COSMO-RS, MST, SMD) as well as on molecular mechanical (MM) point-charge models (GB, PB). The performance of the implicit models was tested by a comparison with experimental water-octanol transfer free energies (AG,) by using single- and multiconformation approaches. MD simulations revealed difficulties in a priori estimation of the flexibility features of the solutes from simple structural descriptors, such as the number of rotatable bonds. An increasing accuracy of the calculated Delta G(ow) was observed in the following order: GB1 similar to PB < GI37 << MST < SMD similar to COSMO-RS with a clear distinction

Název v anglickém jazyce

Assessing the Accuracy and Performance of Implicit Solvent Models for Drug Molecules: Conformational Ensemble Approaches

Popis výsledku anglicky

The accuracy and performance of implicit solvent methods for solvation free energy calculations were assessed on a set of 20 neutral drug molecules. Molecular dynamics (MD) provided ensembles of conformations in water and water saturated octanol. The solvation free energies were calculated by popular implicit solvent models based on quantum mechanical (QM) electronic densities (COSMO-RS, MST, SMD) as well as on molecular mechanical (MM) point-charge models (GB, PB). The performance of the implicit models was tested by a comparison with experimental water-octanol transfer free energies (AG,) by using single- and multiconformation approaches. MD simulations revealed difficulties in a priori estimation of the flexibility features of the solutes from simple structural descriptors, such as the number of rotatable bonds. An increasing accuracy of the calculated Delta G(ow) was observed in the following order: GB1 similar to PB < GI37 << MST < SMD similar to COSMO-RS with a clear distinction

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2013

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Physical Chemistry B

ISSN

1520-6106

e-ISSN

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Svazek periodika

117

Číslo periodika v rámci svazku

19

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

5950-5962

Kód UT WoS článku

000319649800017

EID výsledku v databázi Scopus

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