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Recent advances in QM/MM free energy calculations using reference potentials

Duarte, Fernanda ; Amrein, Beat A ; Blaha-Nelson, David and Kamerlin, Shina C L LU orcid (2015) In Biochimica et Biophysica Acta 1850(5). p.954-965
Abstract

BACKGROUND: Recent years have seen enormous progress in the development of methods for modeling (bio)molecular systems. This has allowed for the simulation of ever larger and more complex systems. However, as such complexity increases, the requirements needed for these models to be accurate and physically meaningful become more and more difficult to fulfill. The use of simplified models to describe complex biological systems has long been shown to be an effective way to overcome some of the limitations associated with this computational cost in a rational way.

SCOPE OF REVIEW: Hybrid QM/MM approaches have rapidly become one of the most popular computational tools for studying chemical reactivity in biomolecular systems. However,... (More)

BACKGROUND: Recent years have seen enormous progress in the development of methods for modeling (bio)molecular systems. This has allowed for the simulation of ever larger and more complex systems. However, as such complexity increases, the requirements needed for these models to be accurate and physically meaningful become more and more difficult to fulfill. The use of simplified models to describe complex biological systems has long been shown to be an effective way to overcome some of the limitations associated with this computational cost in a rational way.

SCOPE OF REVIEW: Hybrid QM/MM approaches have rapidly become one of the most popular computational tools for studying chemical reactivity in biomolecular systems. However, the high cost involved in performing high-level QM calculations has limited the applicability of these approaches when calculating free energies of chemical processes. In this review, we present some of the advances in using reference potentials and mean field approximations to accelerate high-level QM/MM calculations. We present illustrative applications of these approaches and discuss challenges and future perspectives for the field.

MAJOR CONCLUSIONS: The use of physically-based simplifications has shown to effectively reduce the cost of high-level QM/MM calculations. In particular, lower-level reference potentials enable one to reduce the cost of expensive free energy calculations, thus expanding the scope of problems that can be addressed.

GENERAL SIGNIFICANCE: As was already demonstrated 40 years ago, the usage of simplified models still allows one to obtain cutting edge results with substantially reduced computational cost. This article is part of a Special Issue entitled Recent developments of molecular dynamics.

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author
; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Chlorides/chemistry, Energy Transfer, Ethylene Dichlorides/chemistry, Hydrolases/chemistry, Kinetics, Methyl Chloride/chemistry, Molecular Dynamics Simulation/standards, Protein Conformation, Protein Folding, Protein Stability, Protein Unfolding, Proteins/chemistry, Reference Standards, Structure-Activity Relationship, Surface Properties, Thermodynamics, Uracil/chemistry
in
Biochimica et Biophysica Acta
volume
1850
issue
5
pages
12 pages
publisher
Elsevier
external identifiers
  • scopus:84923124949
  • pmid:25038480
ISSN
0006-3002
DOI
10.1016/j.bbagen.2014.07.008
language
English
LU publication?
no
additional info
Copyright © 2014. Published by Elsevier B.V.
id
e2455fbc-efa5-4638-b330-09f5de4c7b22
date added to LUP
2025-01-11 21:53:04
date last changed
2025-07-13 18:51:24
@article{e2455fbc-efa5-4638-b330-09f5de4c7b22,
  abstract     = {{<p>BACKGROUND: Recent years have seen enormous progress in the development of methods for modeling (bio)molecular systems. This has allowed for the simulation of ever larger and more complex systems. However, as such complexity increases, the requirements needed for these models to be accurate and physically meaningful become more and more difficult to fulfill. The use of simplified models to describe complex biological systems has long been shown to be an effective way to overcome some of the limitations associated with this computational cost in a rational way.</p><p>SCOPE OF REVIEW: Hybrid QM/MM approaches have rapidly become one of the most popular computational tools for studying chemical reactivity in biomolecular systems. However, the high cost involved in performing high-level QM calculations has limited the applicability of these approaches when calculating free energies of chemical processes. In this review, we present some of the advances in using reference potentials and mean field approximations to accelerate high-level QM/MM calculations. We present illustrative applications of these approaches and discuss challenges and future perspectives for the field.</p><p>MAJOR CONCLUSIONS: The use of physically-based simplifications has shown to effectively reduce the cost of high-level QM/MM calculations. In particular, lower-level reference potentials enable one to reduce the cost of expensive free energy calculations, thus expanding the scope of problems that can be addressed.</p><p>GENERAL SIGNIFICANCE: As was already demonstrated 40 years ago, the usage of simplified models still allows one to obtain cutting edge results with substantially reduced computational cost. This article is part of a Special Issue entitled Recent developments of molecular dynamics.</p>}},
  author       = {{Duarte, Fernanda and Amrein, Beat A and Blaha-Nelson, David and Kamerlin, Shina C L}},
  issn         = {{0006-3002}},
  keywords     = {{Chlorides/chemistry; Energy Transfer; Ethylene Dichlorides/chemistry; Hydrolases/chemistry; Kinetics; Methyl Chloride/chemistry; Molecular Dynamics Simulation/standards; Protein Conformation; Protein Folding; Protein Stability; Protein Unfolding; Proteins/chemistry; Reference Standards; Structure-Activity Relationship; Surface Properties; Thermodynamics; Uracil/chemistry}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{954--965}},
  publisher    = {{Elsevier}},
  series       = {{Biochimica et Biophysica Acta}},
  title        = {{Recent advances in QM/MM free energy calculations using reference potentials}},
  url          = {{http://dx.doi.org/10.1016/j.bbagen.2014.07.008}},
  doi          = {{10.1016/j.bbagen.2014.07.008}},
  volume       = {{1850}},
  year         = {{2015}},
}