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Electrostatic embedding in large-scale first principles quantum mechanical calculations on biomolecules

Electrostatic embedding in large-scale first principles quantum mechanical calculations on biomolecules
Electrostatic embedding in large-scale first principles quantum mechanical calculations on biomolecules
Biomolecular simulations with atomistic detail are often required to describe interactions with chemical accuracy for applications such as the calculation of free energies of binding or chemical reactions in enzymes. Force fields are typically used for this task but these rely on extensive parameterisation which in cases can lead to limited accuracy and transferability, for example for ligands with unusual functional groups. These limitations can be overcome with first principles calculations with methods such as density functional theory (DFT) but at a much higher computational cost. The use of electrostatic embedding can significantly reduce this cost by representing a portion of the simulated system in terms of highly localised charge distributions. These classical charge distributions are electrostatically coupled with the quantum system and represent the effect of the environment in which the quantum system is embedded. In this paper we describe and evaluate such an embedding scheme in which the polarisation of the electronic density by the embedding charges occurs self-consistently during the calculation of the density. We have implemented this scheme in a linear-scaling DFT program as our aim is to treat with DFT entire biomolecules (such as proteins) and large portions of the solvent. We test this approach in the calculation of interaction energies of ligands with biomolecules and solvent and investigate under what conditions these can be obtained with the same level of accuracy as when the entire system is described by DFT, for a variety of neutral and charged species
0021-9606
224107-[13pp]
Fox, Stephen J.
a8957e8a-3086-4917-8575-eb0f9e8604cf
Pittock, Chris
0732d958-6ae6-48d8-81c8-3d17e32a0039
Fox, Thomas
04c97900-df28-4af0-a7ca-62e5efcfcaba
Tautermann, Christofer S.
f35b4fb9-df35-4e57-8d68-8e20b5a177fd
Malcolm, Noj
936a21b1-8f9e-43d3-b7ca-86dd305c28cf
Skylaris, Chris-Kriton
8f593d13-3ace-4558-ba08-04e48211af61
Fox, Stephen J.
a8957e8a-3086-4917-8575-eb0f9e8604cf
Pittock, Chris
0732d958-6ae6-48d8-81c8-3d17e32a0039
Fox, Thomas
04c97900-df28-4af0-a7ca-62e5efcfcaba
Tautermann, Christofer S.
f35b4fb9-df35-4e57-8d68-8e20b5a177fd
Malcolm, Noj
936a21b1-8f9e-43d3-b7ca-86dd305c28cf
Skylaris, Chris-Kriton
8f593d13-3ace-4558-ba08-04e48211af61

Fox, Stephen J., Pittock, Chris, Fox, Thomas, Tautermann, Christofer S., Malcolm, Noj and Skylaris, Chris-Kriton (2011) Electrostatic embedding in large-scale first principles quantum mechanical calculations on biomolecules. The Journal of Chemical Physics, 135 (22), 224107-[13pp]. (doi:10.1063/1.3665893).

Record type: Article

Abstract

Biomolecular simulations with atomistic detail are often required to describe interactions with chemical accuracy for applications such as the calculation of free energies of binding or chemical reactions in enzymes. Force fields are typically used for this task but these rely on extensive parameterisation which in cases can lead to limited accuracy and transferability, for example for ligands with unusual functional groups. These limitations can be overcome with first principles calculations with methods such as density functional theory (DFT) but at a much higher computational cost. The use of electrostatic embedding can significantly reduce this cost by representing a portion of the simulated system in terms of highly localised charge distributions. These classical charge distributions are electrostatically coupled with the quantum system and represent the effect of the environment in which the quantum system is embedded. In this paper we describe and evaluate such an embedding scheme in which the polarisation of the electronic density by the embedding charges occurs self-consistently during the calculation of the density. We have implemented this scheme in a linear-scaling DFT program as our aim is to treat with DFT entire biomolecules (such as proteins) and large portions of the solvent. We test this approach in the calculation of interaction energies of ligands with biomolecules and solvent and investigate under what conditions these can be obtained with the same level of accuracy as when the entire system is described by DFT, for a variety of neutral and charged species

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Published date: December 2011
Organisations: Computational Systems Chemistry

Identifiers

Local EPrints ID: 336974
URI: http://eprints.soton.ac.uk/id/eprint/336974
ISSN: 0021-9606
PURE UUID: 06a2c92f-4e2b-404f-95a8-79c1e8a56fe5
ORCID for Chris-Kriton Skylaris: ORCID iD orcid.org/0000-0003-0258-3433

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Date deposited: 12 Apr 2012 14:07
Last modified: 15 Mar 2024 03:26

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Contributors

Author: Stephen J. Fox
Author: Chris Pittock
Author: Thomas Fox
Author: Christofer S. Tautermann
Author: Noj Malcolm

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