Exponential Repulsion Improves Structural Predictability of Molecular Docking

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F16%3A00467239" target="_blank" >RIV/61389030:_____/16:00467239 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/16:33160156

Výsledek na webu

<a href="http://dx.doi.org/10.1002/jcc.24473" target="_blank" >http://dx.doi.org/10.1002/jcc.24473</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/jcc.24473" target="_blank" >10.1002/jcc.24473</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Exponential Repulsion Improves Structural Predictability of Molecular Docking

Popis výsledku v původním jazyce

Molecular docking is a powerful tool for theoretical prediction of the preferred conformation and orientation of small molecules within protein active sites. The obtained poses can be used for estimation of binding energies, which indicate the inhibition effect of designed inhibitors, and therefore might be used for in silico drug design. However, the evaluation of ligand binding affinity critically depends on successful prediction of the native binding mode. Contemporary docking methods are often based on scoring functions derived from molecular mechanical potentials. In such potentials, nonbonded interactions are typically represented by electrostatic interactions between atom-centered partial charges and standard 6-12 Lennard-Jones potential. Here, we present implementation and testing of a scoring function based on more physically justified exponential repulsion instead of the standard Lennard-Jones potential. We found that this scoring function significantly improved prediction of the native binding modes in proteins bearing narrow active sites such as serine proteases and kinases.

Název v anglickém jazyce

Exponential Repulsion Improves Structural Predictability of Molecular Docking

Popis výsledku anglicky

Molecular docking is a powerful tool for theoretical prediction of the preferred conformation and orientation of small molecules within protein active sites. The obtained poses can be used for estimation of binding energies, which indicate the inhibition effect of designed inhibitors, and therefore might be used for in silico drug design. However, the evaluation of ligand binding affinity critically depends on successful prediction of the native binding mode. Contemporary docking methods are often based on scoring functions derived from molecular mechanical potentials. In such potentials, nonbonded interactions are typically represented by electrostatic interactions between atom-centered partial charges and standard 6-12 Lennard-Jones potential. Here, we present implementation and testing of a scoring function based on more physically justified exponential repulsion instead of the standard Lennard-Jones potential. We found that this scoring function significantly improved prediction of the native binding modes in proteins bearing narrow active sites such as serine proteases and kinases.

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

<a href="/cs/project/LO1305" target="_blank" >LO1305: Rozvoj centra pokročilých technologií a materiálů</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Journal of Computational Chemistry

ISSN

0192-8651

e-ISSN

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Svazek periodika

37

Číslo periodika v rámci svazku

28

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

2485-2494

Kód UT WoS článku

000387484200001

EID výsledku v databázi Scopus

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