Comparison of Molecular Recognition in Docking Versus Experimental CSD and PDB Data
Molecular docking is a widely used technique in structure-based drug design for generating poses of small molecules in a protein receptor structure. These poses are then ranked to prioritize compounds for experimental validation. Numerous approaches to assessing the structural fit of a ligand exist,...
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| مؤلفون آخرون: | |
| منشور في: |
2025
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| _version_ | 1852018506599497728 |
|---|---|
| author | Andreas Tosstorff (8250999) |
| author2 | Bernd Kuhn (260084) |
| author2_role | author |
| author_facet | Andreas Tosstorff (8250999) Bernd Kuhn (260084) |
| author_role | author |
| dc.creator.none.fl_str_mv | Andreas Tosstorff (8250999) Bernd Kuhn (260084) |
| dc.date.none.fl_str_mv | 2025-07-14T15:48:11Z |
| dc.identifier.none.fl_str_mv | 10.1021/acs.jcim.5c00893.s006 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/dataset/Comparison_of_Molecular_Recognition_in_Docking_Versus_Experimental_CSD_and_PDB_Data/29562171 |
| dc.rights.none.fl_str_mv | CC BY-NC 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biophysics Biochemistry Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified Physical Sciences not elsewhere classified Information Systems not elsewhere classified widely used technique underestimated electrostatic repulsion simple scoring functions prioritization method chosen identify potential deficiencies energy hydroxyl conformations based drug design analysis allows us future docking algorithms torsional ligand strain pose scoring approach docking algorithm vina protein receptor structure compare poses generated docking algorithm ligand exist experimental pose structural fit small molecules significantly improves prioritize compounds numerous approaches molecular recognition inspire improvements generating poses experimental validation docked poses crystallographic data |
| dc.title.none.fl_str_mv | Comparison of Molecular Recognition in Docking Versus Experimental CSD and PDB Data |
| dc.type.none.fl_str_mv | Dataset info:eu-repo/semantics/publishedVersion dataset |
| description | Molecular docking is a widely used technique in structure-based drug design for generating poses of small molecules in a protein receptor structure. These poses are then ranked to prioritize compounds for experimental validation. Numerous approaches to assessing the structural fit of a ligand exist, ranging from simple scoring functions to more elaborate free energy calculations. Regardless of the prioritization method chosen, its accuracy is limited by the quality of the protein–ligand pose. Here, we apply two established statistical approaches for quantifying atomic interaction preferences and torsional ligand strain, respectively, to compare poses generated by the docking algorithm Vina with crystallographic data from the PDB and CSD. This analysis allows us to identify potential deficiencies in the docking algorithm, such as underestimated electrostatic repulsion or high-energy hydroxyl conformations. By highlighting such inaccuracies, we aim to inspire improvements in future docking algorithms. Finally, a pose scoring approach is proposed that significantly improves the retrieval of the experimental pose from a set of docked poses. |
| eu_rights_str_mv | openAccess |
| id | Manara_9bcce6afdbb041ffdee2770bbb1c2f95 |
| identifier_str_mv | 10.1021/acs.jcim.5c00893.s006 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/29562171 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY-NC 4.0 |
| spelling | Comparison of Molecular Recognition in Docking Versus Experimental CSD and PDB DataAndreas Tosstorff (8250999)Bernd Kuhn (260084)BiophysicsBiochemistryBiological Sciences not elsewhere classifiedChemical Sciences not elsewhere classifiedPhysical Sciences not elsewhere classifiedInformation Systems not elsewhere classifiedwidely used techniqueunderestimated electrostatic repulsionsimple scoring functionsprioritization method chosenidentify potential deficienciesenergy hydroxyl conformationsbased drug designanalysis allows usfuture docking algorithmstorsional ligand strainpose scoring approachdocking algorithm vinaprotein receptor structurecompare poses generateddocking algorithmligand existexperimental posestructural fitsmall moleculessignificantly improvesprioritize compoundsnumerous approachesmolecular recognitioninspire improvementsgenerating posesexperimental validationdocked posescrystallographic dataMolecular docking is a widely used technique in structure-based drug design for generating poses of small molecules in a protein receptor structure. These poses are then ranked to prioritize compounds for experimental validation. Numerous approaches to assessing the structural fit of a ligand exist, ranging from simple scoring functions to more elaborate free energy calculations. Regardless of the prioritization method chosen, its accuracy is limited by the quality of the protein–ligand pose. Here, we apply two established statistical approaches for quantifying atomic interaction preferences and torsional ligand strain, respectively, to compare poses generated by the docking algorithm Vina with crystallographic data from the PDB and CSD. This analysis allows us to identify potential deficiencies in the docking algorithm, such as underestimated electrostatic repulsion or high-energy hydroxyl conformations. By highlighting such inaccuracies, we aim to inspire improvements in future docking algorithms. Finally, a pose scoring approach is proposed that significantly improves the retrieval of the experimental pose from a set of docked poses.2025-07-14T15:48:11ZDatasetinfo:eu-repo/semantics/publishedVersiondataset10.1021/acs.jcim.5c00893.s006https://figshare.com/articles/dataset/Comparison_of_Molecular_Recognition_in_Docking_Versus_Experimental_CSD_and_PDB_Data/29562171CC BY-NC 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/295621712025-07-14T15:48:11Z |
| spellingShingle | Comparison of Molecular Recognition in Docking Versus Experimental CSD and PDB Data Andreas Tosstorff (8250999) Biophysics Biochemistry Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified Physical Sciences not elsewhere classified Information Systems not elsewhere classified widely used technique underestimated electrostatic repulsion simple scoring functions prioritization method chosen identify potential deficiencies energy hydroxyl conformations based drug design analysis allows us future docking algorithms torsional ligand strain pose scoring approach docking algorithm vina protein receptor structure compare poses generated docking algorithm ligand exist experimental pose structural fit small molecules significantly improves prioritize compounds numerous approaches molecular recognition inspire improvements generating poses experimental validation docked poses crystallographic data |
| status_str | publishedVersion |
| title | Comparison of Molecular Recognition in Docking Versus Experimental CSD and PDB Data |
| title_full | Comparison of Molecular Recognition in Docking Versus Experimental CSD and PDB Data |
| title_fullStr | Comparison of Molecular Recognition in Docking Versus Experimental CSD and PDB Data |
| title_full_unstemmed | Comparison of Molecular Recognition in Docking Versus Experimental CSD and PDB Data |
| title_short | Comparison of Molecular Recognition in Docking Versus Experimental CSD and PDB Data |
| title_sort | Comparison of Molecular Recognition in Docking Versus Experimental CSD and PDB Data |
| topic | Biophysics Biochemistry Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified Physical Sciences not elsewhere classified Information Systems not elsewhere classified widely used technique underestimated electrostatic repulsion simple scoring functions prioritization method chosen identify potential deficiencies energy hydroxyl conformations based drug design analysis allows us future docking algorithms torsional ligand strain pose scoring approach docking algorithm vina protein receptor structure compare poses generated docking algorithm ligand exist experimental pose structural fit small molecules significantly improves prioritize compounds numerous approaches molecular recognition inspire improvements generating poses experimental validation docked poses crystallographic data |