A robust force field based method for calculating conformational energies of charged drug-like molecules

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Standard

A robust force field based method for calculating conformational energies of charged drug-like molecules. / Pøhlsgaard, Jacob; Harpsøe, Kasper; Jørgensen, Flemming Steen; Olsen, Lars.

I: Journal of Chemical Information and Modeling, Bind 52, Nr. 2, 2012, s. 409-419.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Pøhlsgaard, J, Harpsøe, K, Jørgensen, FS & Olsen, L 2012, 'A robust force field based method for calculating conformational energies of charged drug-like molecules', Journal of Chemical Information and Modeling, bind 52, nr. 2, s. 409-419. https://doi.org/10.1021/ci200345f

APA

Pøhlsgaard, J., Harpsøe, K., Jørgensen, F. S., & Olsen, L. (2012). A robust force field based method for calculating conformational energies of charged drug-like molecules. Journal of Chemical Information and Modeling, 52(2), 409-419. https://doi.org/10.1021/ci200345f

Vancouver

Pøhlsgaard J, Harpsøe K, Jørgensen FS, Olsen L. A robust force field based method for calculating conformational energies of charged drug-like molecules. Journal of Chemical Information and Modeling. 2012;52(2):409-419. https://doi.org/10.1021/ci200345f

Author

Pøhlsgaard, Jacob ; Harpsøe, Kasper ; Jørgensen, Flemming Steen ; Olsen, Lars. / A robust force field based method for calculating conformational energies of charged drug-like molecules. I: Journal of Chemical Information and Modeling. 2012 ; Bind 52, Nr. 2. s. 409-419.

Bibtex

@article{35a87eadb2da4fcaa76fc49f3e8728ff,
title = "A robust force field based method for calculating conformational energies of charged drug-like molecules",
abstract = "The binding affinity of a drug like molecule depends among other things on the availability of the bioactive conformation. If the bioactive conformation has a significantly higher energy than the global minimum energy conformation, the molecule is unlikely to bind to its target. Determination of the global minimum energy conformation and calculation of conformational penalties of binding are prerequisites for prediction of reliable binding affinities. Here, we present a simple and computationally efficient procedure to estimate the global energy minimum for a wide variety of structurally diverse molecules, including polar and charged compounds. Identifying global energy minimum conformations of such compounds with force-field methods is problematic due to the exaggeration of intramolecular electrostatic interactions. We demonstrate that the global energy minimum conformations of zwitterionic compounds generated by conformational analysis with modified electrostatics are good approximations of the conformational distributions predicted by experimental data and in simulated annealing performed in explicit solvent.",
keywords = "The Faculty of Pharmaceutical Sciences",
author = "Jacob P{\o}hlsgaard and Kasper Harps{\o}e and J{\o}rgensen, {Flemming Steen} and Lars Olsen",
year = "2012",
doi = "10.1021/ci200345f",
language = "English",
volume = "52",
pages = "409--419",
journal = "Journal of Chemical Information and Modeling",
issn = "1549-9596",
publisher = "American Chemical Society",
number = "2",

}

RIS

TY - JOUR

T1 - A robust force field based method for calculating conformational energies of charged drug-like molecules

AU - Pøhlsgaard, Jacob

AU - Harpsøe, Kasper

AU - Jørgensen, Flemming Steen

AU - Olsen, Lars

PY - 2012

Y1 - 2012

N2 - The binding affinity of a drug like molecule depends among other things on the availability of the bioactive conformation. If the bioactive conformation has a significantly higher energy than the global minimum energy conformation, the molecule is unlikely to bind to its target. Determination of the global minimum energy conformation and calculation of conformational penalties of binding are prerequisites for prediction of reliable binding affinities. Here, we present a simple and computationally efficient procedure to estimate the global energy minimum for a wide variety of structurally diverse molecules, including polar and charged compounds. Identifying global energy minimum conformations of such compounds with force-field methods is problematic due to the exaggeration of intramolecular electrostatic interactions. We demonstrate that the global energy minimum conformations of zwitterionic compounds generated by conformational analysis with modified electrostatics are good approximations of the conformational distributions predicted by experimental data and in simulated annealing performed in explicit solvent.

AB - The binding affinity of a drug like molecule depends among other things on the availability of the bioactive conformation. If the bioactive conformation has a significantly higher energy than the global minimum energy conformation, the molecule is unlikely to bind to its target. Determination of the global minimum energy conformation and calculation of conformational penalties of binding are prerequisites for prediction of reliable binding affinities. Here, we present a simple and computationally efficient procedure to estimate the global energy minimum for a wide variety of structurally diverse molecules, including polar and charged compounds. Identifying global energy minimum conformations of such compounds with force-field methods is problematic due to the exaggeration of intramolecular electrostatic interactions. We demonstrate that the global energy minimum conformations of zwitterionic compounds generated by conformational analysis with modified electrostatics are good approximations of the conformational distributions predicted by experimental data and in simulated annealing performed in explicit solvent.

KW - The Faculty of Pharmaceutical Sciences

U2 - 10.1021/ci200345f

DO - 10.1021/ci200345f

M3 - Journal article

VL - 52

SP - 409

EP - 419

JO - Journal of Chemical Information and Modeling

JF - Journal of Chemical Information and Modeling

SN - 1549-9596

IS - 2

ER -

ID: 35359657