Conformational Free Energy Modeling of Druglike Molecules by Metadynamics in the WHIM Space

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F12%3A43893974" target="_blank" >RIV/60461373:22330/12:43893974 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1021/ci200623n" target="_blank" >http://dx.doi.org/10.1021/ci200623n</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/ci200623n" target="_blank" >10.1021/ci200623n</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Conformational Free Energy Modeling of Druglike Molecules by Metadynamics in the WHIM Space

Popis výsledku v původním jazyce

Protein-ligand affinities can be significantly influenced not only by the interaction itself but also by conformational equilibrium of both binding partners, free ligand and free protein. Identification of important conformational families of a ligand and prediction of their thermodynamics is important for efficient ligand design. Here we report conformational free energy modeling of nine small-molecule drugs in explicitly modeled water by metadynamics with a bias potential applied in the space of weighted holistic invariant molecular (WHIM) descriptors. Application of metadynamics enhances conformational sampling compared to unbiased molecular dynamics simulation and allows to predict relative free energies of key conformations. Selected free energy minima and one example of transition state were tested by a series of unbiased molecular dynamics simulation. Comparison of free energy surfaces of free and target-bound Imatinib provides an estimate of free energy penalty of conformationa

Název v anglickém jazyce

Conformational Free Energy Modeling of Druglike Molecules by Metadynamics in the WHIM Space

Popis výsledku anglicky

Protein-ligand affinities can be significantly influenced not only by the interaction itself but also by conformational equilibrium of both binding partners, free ligand and free protein. Identification of important conformational families of a ligand and prediction of their thermodynamics is important for efficient ligand design. Here we report conformational free energy modeling of nine small-molecule drugs in explicitly modeled water by metadynamics with a bias potential applied in the space of weighted holistic invariant molecular (WHIM) descriptors. Application of metadynamics enhances conformational sampling compared to unbiased molecular dynamics simulation and allows to predict relative free energies of key conformations. Selected free energy minima and one example of transition state were tested by a series of unbiased molecular dynamics simulation. Comparison of free energy surfaces of free and target-bound Imatinib provides an estimate of free energy penalty of conformationa

Druh

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

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

—

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2012

Kód důvěrnosti údajů

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

Název periodika

Journal of Chemical Information and Modeling

ISSN

1549-9596

e-ISSN

—

Svazek periodika

52

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

804-813

Kód UT WoS článku

000301884400015

EID výsledku v databázi Scopus

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