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Cited by 318Computational Drug Discovery MethodsProtein Structure and DynamicsAdvanced Chemical Physics Studies

AutoDock4Zn: An Improved AutoDock Force Field for Small-Molecule Docking to Zinc Metalloproteins

Open access
Santos-Martins, Diogo, Forli, Stefano, Ramos, Maria João, Olson, Arthur J.·2014·Journal of Chemical Information and Modeling
DOI 10.1021/ci500209ePMC PMC4144784
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Abstract

Zinc is present in a wide variety of proteins and is important in the metabolism of most organisms. Zinc metalloenzymes are therapeutically relevant targets in diseases such as cancer, heart disease, bacterial infection, and Alzheimer's disease. In most cases a drug molecule targeting such enzymes establishes an interaction that coordinates with the zinc ion. Thus, accurate prediction of the interaction of ligands with zinc is an important aspect of computational docking and virtual screening against zinc containing proteins. We have extended the AutoDock force field to include a specialized potential describing the interactions of zinc-coordinating ligands. This potential describes both the energetic and geometric components of the interaction. The new force field, named AutoDock4Zn, was calibrated on a data set of 292 crystal complexes containing zinc. Redocking experiments show that the force field provides significant improvement in performance in both free energy of binding estimation as well as in root-mean-square deviation from the crystal structure pose. The new force field has been implemented in AutoDock without modification to the source code.

Integrity signals

Registry

Crossref · 10.1021/ci500209e

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

10 of 36 cited sources checked · 2 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    That nonbonded description depends on assigned partial charges, so its accuracy is strongly tied to the charge model chosen.

    “This description relies on assignment of partial charges,11−13 and thus accuracy becomes strongly dependent on the choice of charge model.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [11] Stote R. H., 1995, Proteins: Struct., Funct., Bioinf. source
    • cites [12] Wu R., 2011, J. Chem. Theory Comput. source

      The Methods section defines the nonbonded SLEF interaction using the zinc charge and each other atom’s MM charge; the Discussion says its behavior varies with charge magnitude. The paper does not establish that accuracy is strongly dependent on the choice of charge model. Its Introduction instead identifies the conventional 1/r interaction form as the main deficiency of existing nonbonded models. No page numbers are available in our copy. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [13] Hu X., 2003, J. Molec. Graph. Modell. source
  • Premisecitation

    An electrostatic model based on the filled valence orbital of Zn2+ cannot explain why histidine and cysteine are more common zinc-coordinating residues than the more electronegative carboxylates of glutamate and aspartate.

    “Also, an electrostatic model based on the filled valence orbital of the Zn2+ ion fails to explain the prevalence of histidine and cysteine over the more electronegative carboxylate groups of glutamate and aspartate as the most frequent zinc coordinating residues.14−17”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [14] Andreini C., 2012, J. Inorg. Biochem. source
    • cites [15] Patel K., 2007, Biochim. Biophy. Acta source
    • cites [16] Alberts I. L., 1998, Protein Sci. source

      Section 2 (page unavailable) reports the frequency of zinc-coordinating residues in Figure 1, and the coordination-geometry discussion says histidine predominates in mono-zinc sites. Our copy does not establish the claimed overall comparison for both histidine and cysteine against glutamate and aspartate, or say that a filled-valence-orbital electrostatic model fails to explain it. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [17] Laitaoja M., 2013, Inorg. Chem. source
  • Premisecitation

    Dockings using the hydrated ligand protocol consistently predicted that waters would be displaced.

    “In fact, dockings performed with the hydrated ligand protocol30 consistently predicted the displacement of the waters.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [30] Forli S., 2012, J. Med. Chem. source

      The Results and discussion > Case studies passage reports that hydrated docking predicted displacement of water A for one ligand and conserved water B. It supports the protocol's ability to predict displacement, but not that its dockings consistently predicted displacement of the waters; the paper says the outcome depends on the ligand. Page numbers were not available in our copy. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Premisecitation

    Spherical potentials are especially suitable for accurately reproducing hydroxamate coordination geometries.

    “Spherical potentials are particularly suitable for accurately reproducing hydroxamate coordination geometries.39,40”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [39] Wu R., 2011, J. Am. Chem. Soc. source

      The paper’s discussion of QM/MM simulations says they reproduced hydroxamate coordination configurations in HDAC8 and HDAC7, but it does not identify spherical potentials as the method responsible. Searches for spherical potentials and their suitability for reproducing coordination geometry found no passage addressing that claim (page unavailable in our copy). (LLM, conf=0.73)

      Experimental — accuracy not yet measured
    • cites [40] Chiu Y.-H., 2005, Inorg. Chem. source
  • Premisecitation

    Bonded models, such as the Zinc AMBER Force Field, represent tetrahedral coordination with harmonic potentials and angle terms for an explicit bond, giving directionality.

    “Bonded models, such as the Zinc AMBER Force Field,23 describe the tetrahedral coordination with harmonic potentials and angle terms for an explicit bond that provides directionality.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [23] Peters M. B., 2010, J. Chem. Theory Comput. source
  • May combine two claims. 28
  • Classified as probably not a substantial claim. 16
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    Some potent inhibitors coordinate Zn2+ through uncharged nitrogens with lone pairs, such as sulfonamides and imidazoles, and these appear to bind more strongly than negatively charged nitro groups.

    “Moreover, some high potency inhibitors coordinate Zn2+ via uncharged nitrogens with electron lone pairs, such as those found in sulfonamides18 and imidazoles6 (see Figure 13), that seem to interact more strongly than negatively charged nitro groups.7”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [18] Håkansson K., 1994, FEBS Lett. source

      The citation to this paper is attached to the sulfonamide example, not the separate imidazole or nitro-group claims. In Results and discussion (page not specified in our copy), the paper says the sulfonamide inhibitor binds zinc through a negatively charged nitrogen, contrary to the claim that this nitrogen is uncharged. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [6] Reid T. S., 2004, Biochemistry source
    • cites [7] Docquier J.-D., 2010, Antimicrob. Agents Chemother. source

  • Classified as probably not a substantial claim.

    Premisecitation

    The standard AutoDock force field computes free energy of binding as a weighted sum of van der Waals, hydrogen bond, Coulomb electrostatic, desolvation, and ligand torsional entropy terms, with weights estimated by linear regression.

    “The standard force field includes the following terms (eq 1):371where the free energy of binding (FEB) is calculated as a sum of van der Waals (vdW), hydrogen bond (Hbond), Coulomb electrostatic (Elec), desolvation (desolv) and ligand torsional entropy (torsDoF); each term is weighted by a specific value (Wterm) estimated using a linear regression model.37”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [37] Huey R., 2007, J. Comput. Chem. source

      The Overview (page unavailable) describes van der Waals-like dispersion/repulsion, hydrogen-bond, electrostatic and desolvation terms, plus a weighted torsional-entropy term. It says the weights are optimized against experimentally characterized complexes, but our copy does not specify linear regression as the estimation method. (LLM, conf=0.78)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In the Gasteiger charge model used by AutoDock, oxygen atoms receive more negative charges than nitrogen and sulfur, making oxygen the preferred chelator of positively charged metals.

    “Also, in the Gasteiger38 charge model used in AutoDock,37 oxygen atoms are systematically assigned a more negative charge than nitrogen and sulfur, thus resulting in the preferred candidates for chelating positively charged metal.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [38] Gasteiger J., 1980, Tetrahedron source
    • cites [37] Huey R., 2007, J. Comput. Chem. source

      The Coordinate Sets section says the authors assigned atomic charges using the Gasteiger PEOE method and processed ligands with AutoDock tools. The Magnitude of Terms section says metal-ion electrostatic interactions can be strongly favorable. Neither section says Gasteiger systematically assigns oxygen a more negative charge than nitrogen or sulfur, or that this makes oxygen the preferred metal chelator; page numbers are unavailable in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • The quote only partly states this claim.

    Findingown data

    Filtering Binding MOAD for complexes with at least one zinc ion, experimental Ki or Kd values, no ligand alternate conformations or missing atoms, and no alternate side-chain conformations in receptor residues within 5 Å of any ligand atom yielded 510 complexes downloaded from the Protein Data Bank.

    “This filtering led to a set of 510 complexes, which were downloaded from the Protein Data Bank.32”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [31] Hu L., 2005, Proteins source

      The Introduction and Results and Discussion say Binding MOAD contains protein–ligand complexes obtained from the Protein Data Bank, and the Binding-Affinity Data section reports that some have affinity measurements. They do not report the stated zinc and structural filters or a resulting set of 510 complexes; that count and filtering outcome are not supported by this source. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [32] Bernstein F. C., 1978, Arch. Biochem. Biophys. source

  • May combine two claims.

    Findingown data

    Overall, AutoDock4Zn performed significantly better than both standard AutoDock and Vina force fields.

    “Overall, the new AutoDock4Zn force field performed significantly better than both standard AutoDock and Vina force fields.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Five-coordinated (Zn4,1 and Zn3,2) and six-coordinated (Zn3,3 and Zn4,2) geometries were also present in the data set but were much rarer.

    “Other geometries, like five- (Zn4,1, Zn3,2) and six-coordinated (Zn3,3, Zn4,2), were also found, but were much rarer.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    After filtering, the calibration set contained 292 unique complexes across four coordination classes: Zn3,1, Zn3,2, Zn3,3, Zn4,1, and Zn4,2.

    “This left four coordination classes, Zn3,1, Zn3,2, Zn3,3, Zn4,1, and Zn4,2, resulting in a calibration set of 292 unique complexes.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Zinc is always desolvated in the studied zinc metalloprotein-ligand complexes.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Final force field weights were taken from the last iteration, and the residual standard error was 2.804 kcal/mol.

    “Final force field weights were selected from the last iteration, with a residual standard error was 2.804 kcal/mol.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Standard AutoDock and Vina had roughly the same FEB prediction errors, while AutoDock4Zn improved the success rate by 50% at a threshold below 1.0 kcal/mol.

    “These force fields provide roughly the same prediction errors in FEB estimations, while AutoDock4Zn consistently improved success rate (+50% with <1.0 kcal/mol) (Figure 8).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Analysis of the data set showed that zinc coordination needs a specialized treatment, so the standard AutoDock force field was modified.

    “From our data set analysis, we found that the coordination of zinc requires a specialized treatment, so we modified the standard AutoDock force field.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Zinc is always desolvated in the studied zinc metalloprotein-ligand complexes.

  • May combine two claims.

    Findingown data

    The ligands in the data set span a wide range of structures and binding affinities, making the set suitable for calibrating a force field intended for general use in drug design.

    “The ligands cover a wide range of structure diversity and binding affinity, thus providing an optimal calibration set for generic applicability of the force field for drug design.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For the NEP inhibitor complex with PDB ID 1r1j, AutoDock4 and Vina predicted zinc coordination by the carboxylate group and misaligned the ligand, whereas AutoDock4Zn predicted coordination by sulfanyl and carbonyl groups and gave a more accurate FEB estimate.

    “Both AutoDock4 and Vina predicted zinc to be coordinated by the carboxylate group, resulting in a misalignment of the ligand with respect to the receptor. The AutoDock4Zn, on the other hand, predicted the proper coordination by sulfanyl and carbonyl groups and provided more accurate FEB estimation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Oefner C., 2004, Acta Crystallogr. Sect. D: Biol. Crystallogr. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    The most common coordination geometry in the data set is tetrahedral (Zn3,1 and Zn4,0), which is also the most common geometry in biological systems.

    “The most represented coordination geometry in our data set is the tetrahedral one (Zn3,1, Zn4,0), that was indeed found to be the most common in biological systems.17”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Laitaoja M., 2013, Inorg. Chem. source

  • May combine two claims.

    Findingown data

    AutoDock4Zn improved pose-prediction RMSD accuracy over standard AutoDock and produced results comparable to Vina.

    “The new force field also improves RMSD accuracy over the standard AutoDock force field in pose prediction accuracy (RMSD), producing results comparable with Vina (Figure 9).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    The authors developed AutoDock4Zn, a directional and charge-independent zinc-coordination force field for AutoDock4 that is more accurate than the standard force field.

    “In this paper, we report the development of a directional, charge-independent model for zinc-coordination force field for AutoDock4 which provides higher accuracy than the standard force field.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    The calibration protocol iterated through steps c and d five times to reach convergence, and stable weight values were reached after the first two iterations.

    “The protocol iterated through steps c and d five times to achieve convergence; stable weight values were achieved after the first two iterations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Search complexity and computational power requirements do not increase, so docking speed is unaffected.

    “There is no increase in the search complexity nor in the computational power requirement, therefore docking speed is completely unaffected.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    Because AutoDock4 is fully configurable, the new potential was implemented by modifying standard force field tables and a few Python helper scripts.

    “Due to the fully configurable nature of AutoDock4, the new potential was implemented by modifying the standard force field tables and few Python helper scripts available at http://autodock.scripps.edu/.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The improvements are especially relevant for FEB estimation accuracy and for reproducing proper coordination geometry.

    “Improvements are particularly relevant in the accuracy of FEB estimations, as well as in reproducing the proper coordination geometry.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Premisereasoning

    An accurate description of the ligand-zinc interaction is essential for drug design.

    “thus, an accurate description of this interaction is crucial for drug design.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Proper modeling of zinc coordination requires addressing two issues: the geometry of coordination and the strength of the interaction.

    “To properly model the zinc coordination interactions, two issues should be addressed: the coordination geometry and the interaction strength.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Five serine protease inhibitor complexes in the Zn2,2 class were discarded because zinc is known to be recruited only transiently as a coinhibitor and is not consistently present in the binding site.

    “Finally, 5 complexes involving serine protease inhibitors from Zn2,2 class, were discarded because zinc is known to be recruited transiently as coinhibitor only, and it is not consistently present in the binding site.36”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Katz B. A., 1999, J. Molec. Biol. source

  • May combine two claims.

    Premisecitation

    Carboxylate groups can adopt coordination geometries anywhere between mono- and bidentate, which a discrete classification scheme describes poorly.

    “However, it has been demonstrated that carboxylate groups can adopt any coordination geometry ranging between mono- and bidentate,33,34 which is poorly described by a discrete classification scheme.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [33] Harding M. M., 2001, Acta Crystallogr. Sect. D: Biol. Crystallogr. source
    • cites [34] Ryde U., 1999, Biophys. J. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    For FlexX, coordination geometry accuracy improved, but no improvement in binding energy prediction was reported.

    “However, in this latter case, while improving coordination geometry accuracy, no improvements in binding energy prediction were reported.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Seebeck B., 2008, Proteins: Struct., Funct., Bioinf. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The ε values for the new zinc coordination potential were calibrated independently of each other and of the standard force field terms.

    “The ε values for eq 3 were then calibrated independently from each other and from the other terms in eq 1.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Zinc is always desolvated in the studied zinc metalloprotein-ligand complexes.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All changes to the AutoDock force field were made by adapting the force field table and parameter files, without modifying source code.

    “All modifications to the AutoDock force field were made by adapting the force field table and parameter files, without source code modifications.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Because the standard AutoDock force field lacks specialized terms for metal coordination, it does not account for directionality.

    “Second, due to the lack of a specialized terms for the metal coordination, directionality is not accounted for.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Zinc strongly prefers tetrahedral geometry, and some previously observed variation in coordination spheres is artifactual.

    “It has been recently demonstrated that zinc exhibits a strong preference for the tetrahedral geometry, with some of the previously observed variability in coordination spheres being artifactual.17”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Laitaoja M., 2013, Inorg. Chem. source

  • Classified as probably not a substantial claim.

    Premisecitation

    DFT calculations have been used to calibrate a nondirectional zinc coordination force field that does not depend on atomic partial charges.

    “Recently, DFT calculations were used to calibrate a nondirectional zinc coordination force field independent of atomic partial charges.19”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Pottel J., 2014, J. Chem. Inf. Model. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The data set was split into five bins with approximately uniform distributions of ligand atom types coordinating zinc, and redocking calculations were then performed.

    “The data set was divided in five bins containing an approximately uniform distribution of ligand atom types coordinating zinc, then redocking calculations were performed.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Better docking pose prediction and more accurate identification of coordination geometry led to a more precise FEB estimate.

    “The increase in docking pose prediction and accuracy in the coordination geometry indentification resulted in a more precise FEB estimation (Table 4).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The Zn0,0 class includes complexes where zinc serves only as a crystallization aid, has no biological role, and often surrounds protein structures in large numbers at toxic concentrations.

    “In particular, the Zn0,0 class contains complexes where Zn is used as an aid in crystallization and has no biological significance, surrounding the protein structures often in large number and at toxic concentrations.17”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Laitaoja M., 2013, Inorg. Chem. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    AutoDock's highly customizable architecture allows substantial modifications to be implemented relatively easily and without changing source code.

    “The highly customizable architecture of the program allows implementation of substantial modifications relatively easily and without requiring source code changes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Among nonbonded models, few force fields offer directional potentials; two examples are the cationic dummy atom model and the FlexX scoring function.

    “In nonbonded models, few force fields provide directional potentials. Two examples that do are the cationic dummy atom model5 and the scoring function implemented in FlexX.24”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [5] Pang Y.-P., 1999, Molec. Model. Annual source
    • cites [24] Seebeck B., 2008, Proteins: Struct., Funct., Bioinf. source

  • May combine two claims.

    Premisecitation

    For atoms involved in zinc coordination, standard van der Waals equilibrium distances are much larger than coordination distances; for nitrogen, the vdW equilibrium distance is 2.49 Å versus a coordination distance of 2.0 Å.

    “First, the van der Waals equilibrium distances for the atoms involved in zinc coordination are significantly larger than the coordination distances13,19 (i.e., for nitrogen, the vdW equilibrium distance is 2.49 Å, compared to coordination distance of 2.0 Å).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [13] Hu X., 2003, J. Molec. Graph. Modell. source
    • cites [19] Pottel J., 2014, J. Chem. Inf. Model. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The regression model's predictive ability was assessed by 5-fold cross-validation.

    “Predictive capabilities of the regression model were assessed with 5-fold cross-validation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    The standard AutoDock approach is accurate enough for magnesium ion interactions but not sufficient for describing zinc coordination preferences.

    “While this approach is accurate enough for magnesium ion interactions, it is not sufficient to properly describe zinc coordination preferences.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The increase in accuracy and the absence of computational overhead make AutoDock4Zn suitable for virtual screening campaigns, especially when zinc coordination matters.

    “Therefore, accuracy increase and lack of computational overhead make the AutoDock4Zn suitable for virtual screening campaigns, particularly when coordination of zinc is important.”
    Quote in the paperSubstantial claim
38 of 38

  • The authors state this as an assumption.

    Zinc is always desolvated in the studied zinc metalloprotein-ligand complexes.

    “Therefore, zinc was considered always desolvated, while desolvation energy was implicitly accounted for during the calibration of the force field.”

  • The paper relies on this without support.

    No experimental structures have been reported in which a ligand interacts with zinc through a mediating water molecule.

    “To our knowledge, no experimental structures have been reported where ligands interacted with zinc through the mediation of a water molecule.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The specification and architecture of AutoDock was designed to allow user modification for specialized systems, and has been used previously to model protein flexibility, flexible rings in ligands, zinc interaction, and selective hydration.

    “The specification and architecture of AutoDock was designed to allow this type of user modification for specialized systems, and has been used previously to model protein flexibility, 12 flexible rings in ligands, 13 zinc interaction, 14 and selective hydration.15”

    From Covalent docking using autodock: two-point attractor and flexible side chain methods. (2016) · cites this paper as [14]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Classes listed do not match the count of classes

    Minor

    The text says only four coordination classes remained, but it then lists five classes. That is an internal inconsistency in the description of the final calibration set.

  • Five coordination classes are listed, not four

    Minor

    The stated count is four, but the sentence lists five distinct coordination classes.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Sanner M. F., 1999, J. Mol. Graph Model., 17, 57

Cited by

Sorted by citations

Related

Authors
Santos-Martins, D., Forli, S., Ramos, M. J., & Olson, A. J.
Affiliations
  • Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, United States
  • Scripps Research Institute (US)
  • Universidade do Porto (PT)
Corresponding author
Olson, Arthur J.
ORCID
Venue
Journal of Chemical Information and Modeling
Publisher
American Chemical Society (ACS)
Published
2014-07-18
Volume
54
Issue
8
Pages
2371-2379
ISSN
  • 1549-9596 (ISSN-L)
  • 1549-960X
DOI
10.1021/ci500209e
PMC
PMC4144784
OpenAlex
W2039366858
Cited by
318
References
54
Citations by year
2026: 46 · 2025: 39 · 2024: 35 · 2023: 26 · 2022: 28 · 2021: 28 · 2020: 24 · 2019: 25 · 2018: 22 · 2017: 16 · 2016: 15 · 2015: 12 · 2014: 1
FWCI
16.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Chemical Information and Modeling (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (R01-GM069832)
Topics
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Advanced Chemical Physics Studies
Keywords
force fields, zinc metalloproteins, ligand-metal coordination, zinc metalloenzyme, small molecule docking, virtual screening, binding free energy, force field calibration
MeSH terms
Binding Sites, Humans, Ligands, Metalloproteins, Protein Binding, Software, Structure-Activity Relationship, Thermodynamics, Zinc, Protein Structure, Secondary, Protein Structure, Tertiary, Crystallography, X-Ray, Static Electricity, Molecular Dynamics Simulation, Coordination Complexes, Molecular Docking Simulation

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Claims read under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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