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Energy decomposition analysis based on absolutely localized molecular orbitals for large-scale density functional theory calculations in drug design

Energy decomposition analysis based on absolutely localized molecular orbitals for large-scale density functional theory calculations in drug design
Energy decomposition analysis based on absolutely localized molecular orbitals for large-scale density functional theory calculations in drug design
We report the development and implementation of an energy decomposition analysis (EDA) scheme in the ONETEP linear-scaling electronic structure package. Our approach is hybrid as it combines the localized molecular orbital EDA (Su, P.; Li, H. J. Chem. Phys., 2009, 131, 014102) and the absolutely localized molecular orbital EDA (Khaliullin, R. Z.; et al. J. Phys. Chem. A, 2007, 111, 8753–8765) to partition the intermolecular interaction energy into chemically distinct components (electrostatic, exchange, correlation, Pauli repulsion, polarization, and charge transfer). Limitations shared in EDA approaches such as the issue of basis set dependence in polarization and charge transfer are discussed, and a remedy to this problem is proposed that exploits the strictly localized property of the ONETEP orbitals. Our method is validated on a range of complexes with interactions relevant to drug design. We demonstrate the capabilities for large-scale calculations with our approach on complexes of thrombin with an inhibitor comprised of up to 4975 atoms. Given the capability of ONETEP for large-scale calculations, such as on entire proteins, we expect that our EDA scheme can be applied in a large range of biomolecular problems, especially in the context of drug design.
1549-9618
3135-3148
Phipps, Max
290febb8-7f0a-4bda-9944-96594d6343d2
Fox, T.
1d9ddbf8-6881-48cb-9abb-9c9c74a3f09a
Tautermann, C.S.
8b8df865-08b1-407a-aab9-952445cd4414
Skylaris, Chris
8f593d13-3ace-4558-ba08-04e48211af61
Phipps, Max
290febb8-7f0a-4bda-9944-96594d6343d2
Fox, T.
1d9ddbf8-6881-48cb-9abb-9c9c74a3f09a
Tautermann, C.S.
8b8df865-08b1-407a-aab9-952445cd4414
Skylaris, Chris
8f593d13-3ace-4558-ba08-04e48211af61

Phipps, Max, Fox, T., Tautermann, C.S. and Skylaris, Chris (2016) Energy decomposition analysis based on absolutely localized molecular orbitals for large-scale density functional theory calculations in drug design. Journal of Chemical Theory and Computation, 12 (7), 3135-3148. (doi:10.1021/acs.jctc.6b00272).

Record type: Article

Abstract

We report the development and implementation of an energy decomposition analysis (EDA) scheme in the ONETEP linear-scaling electronic structure package. Our approach is hybrid as it combines the localized molecular orbital EDA (Su, P.; Li, H. J. Chem. Phys., 2009, 131, 014102) and the absolutely localized molecular orbital EDA (Khaliullin, R. Z.; et al. J. Phys. Chem. A, 2007, 111, 8753–8765) to partition the intermolecular interaction energy into chemically distinct components (electrostatic, exchange, correlation, Pauli repulsion, polarization, and charge transfer). Limitations shared in EDA approaches such as the issue of basis set dependence in polarization and charge transfer are discussed, and a remedy to this problem is proposed that exploits the strictly localized property of the ONETEP orbitals. Our method is validated on a range of complexes with interactions relevant to drug design. We demonstrate the capabilities for large-scale calculations with our approach on complexes of thrombin with an inhibitor comprised of up to 4975 atoms. Given the capability of ONETEP for large-scale calculations, such as on entire proteins, we expect that our EDA scheme can be applied in a large range of biomolecular problems, especially in the context of drug design.

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More information

Accepted/In Press date: 1 June 2016
e-pub ahead of print date: 1 June 2016
Published date: 1 June 2016
Organisations: Chemistry, Computational Systems Chemistry

Identifiers

Local EPrints ID: 396999
URI: http://eprints.soton.ac.uk/id/eprint/396999
ISSN: 1549-9618
PURE UUID: adf2cd58-09bd-4ae0-bcfe-558e50a78eda
ORCID for Chris Skylaris: ORCID iD orcid.org/0000-0003-0258-3433

Catalogue record

Date deposited: 17 Jun 2016 13:26
Last modified: 07 Oct 2020 04:54

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