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Cited by 316Computational Drug Discovery MethodsAdvanced Physical and Chemical Molecular InteractionsProtein Structure and Dynamics

The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.

On the use of orientational restraints and symmetry corrections in alchemical free energy calculations

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Mobley, David L., Chodera, John D., Dill, Ken A.·2006·The Journal of Chemical Physics
DOI 10.1063/1.2221683PMC PMC3583553
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Abstract

Alchemical free energy calculations are becoming a useful tool for calculating absolute binding free energies of small molecule ligands to proteins. Here, we find that the presence of multiple metastable ligand orientations can cause convergence problems when distance restraints alone are used. We demonstrate that the use of orientational restraints can greatly accelerate the convergence of these calculations. However, even with this acceleration, we find that sufficient sampling requires substantially longer simulations than are used in many published protocols. To further accelerate convergence, we introduce a new method of configuration space decomposition by orientation which reduces required simulation lengths by at least a factor of 5 in the cases examined. Our method is easily parallelizable, well suited for cases where a ligand cocrystal structure is not available, and can utilize initial orientations generated by docking packages.

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Research works printed but not linked: 11

  1. J. Chem. Theory Comput.
  2. Biophys. J.
  3. 2002, Computer Simulations of Liquids
  4. 1998, Molecular Modeling: Principles and Applications
  5. 1992, Stat. Sci., 7, 457
  6. J. Med. Chem.
  7. 2006, J. Mol. Graphics Modell., 26, 247260
  8. 1980, Math. Comput., 35, 773, 10.2307/2006193 · DOI
  9. 1984, J. Chem. Phys., 81, 3584
  10. 1986, Ann. Stat., 14, 1171
  11. J. Chem. Theory Comput.

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Metadata

Authors
Mobley, D. L., Chodera, J. D., & Dill, K. A.
Affiliations
University of California, San Francisco (US)
ORCID
Venue
The Journal of Chemical Physics
Publisher
AIP Publishing
Published
2006-08-22
Volume
125
Issue
8
Pages
084902-084902
ISSN
  • 0021-9606 (ISSN-L)
  • 1089-7690
DOI
10.1063/1.2221683
PMC
PMC3583553
OpenAlex
W1965762256
Cited by
316
References
50
Citations by year
2026: 6 · 2025: 14 · 2024: 19 · 2023: 18 · 2022: 23 · 2021: 18 · 2020: 18 · 2019: 13 · 2018: 17 · 2017: 15 · 2016: 13 · 2015: 11 · 2014: 17 · 2013: 16 · 2012: 20
FWCI
12.61
Type
journal article
Language
en
Open access
Locations
  • The Journal of Chemical Physics (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of General Medical Sciences (R01GM063592, GM34993, R56GM063592, R01GM034993, GM 063592)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
  • Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Advanced Physical and Chemical Molecular Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
alchemical free energy calculations, absolute binding free energy, protein-ligand binding, convergence acceleration
MeSH terms
Biophysics, Catechols, Chemistry, Physical, Computer Simulation, Crystallization, Ligands, Models, Chemical, Models, Molecular, Models, Theoretical, Molecular Conformation, Proteins, Software, Thermodynamics, Models, Statistical, Phenol

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