ArticleChemMedChem2021
Two Methods, One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses.
Article in ChemMedChem, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Atomistic-Level Insights into the Role of Mutations in the Engineering of PET Hydrolases: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Replacement soaking for human tankyrase 2 enables studies on substrate analogues and inhibitors.Acta crystallographica. Section D, Structural biology · 2026Article
- Developments and challenges in hit progression within fragment-based drug discovery.Nature communications · 2026Review
- Methods for the Investigation of Protein-Ligands Interactions.Advances in experimental medicine and biology · 2026Review
- Using AlphaFold and Symmetrical Docking to Predict Protein-Protein Interactions for Exploring Potential Crystallization Conditions.Proteins · 2025Article
- Di-Journal of medicinal chemistry · 2025Article
- Binding modes of the KRAS(G12C) inhibitors GDC-6036 and LY3537982 revealed by all atom molecular dynamics simulations.Scientific reports · 2025Article
- Myricetin-bound crystal structure of the SARS-CoV-2 helicase NSP13 facilitates the discovery of novel natural inhibitors.Acta crystallographica. Section D, Structural biology · 2025Article
- Revealing protein structures: crystallization of protein-ligand complexes - co-crystallization and crystal soaking.FEBS open bio · 2025Article
- Ascertaining a Structural Basis in Drug Discovery and Development.Journal of medicinal chemistry · 2025Article
- Cryo-EM structures of apo and atorvastatin-bound human 3-hydroxy-3-methylglutaryl-coenzyme A reductase.Acta crystallographica. Section F, Structural biology communications · 2025Article
- Article
- LifeSoaks: a tool for analyzing solvent channels in protein crystals and obstacles for soaking experiments.Acta crystallographica. Section D, Structural biology · 2023Article
- Technologies for Direct Detection of Covalent Protein-Drug Adducts.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Allosteric inhibition of TEM-1 β lactamase: Microsecond molecular dynamics simulations provide mechanistic insights.Protein science : a publication of the Protein Society · 2023Article
- AMX - the highly automated macromolecular crystallography (17-ID-1) beamline at the NSLS-II.Journal of synchrotron radiation · 2022Article
- Large-Scale Ligand Perturbations of the Protein Conformational Landscape Reveal State-Specific Interaction Hotspots.Journal of medicinal chemistry · 2022Article
- Towards design of drugs and delivery systems with the Martini coarse-grained model.QRB discovery · 2022Review
- Two Methods, One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses.ChemMedChem · 2021Article
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Authors and funding
5 authors.
Funding
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Abstract
In lead optimization, protein crystallography is an indispensable tool to analyze drug binding. Binding modes and non-covalent interaction inventories are essential to design follow-up synthesis candidates. Two protocols are commonly applied to produce protein-ligand complexes: cocrystallization and soaking. Because of its time and cost effectiveness, soaking is the more popular method. Taking eight ligand hinge binders of protein kinase A, we demonstrate that cocrystallization is superior. Particularly for flexible proteins, such as kinases, and larger ligands cocrystallization captures more reliable the correct binding pose and induced protein adaptations. The geometrical discrepancies between soaking and cocrystallization appear smaller for fragment-sized ligands. For larger flexible ligands that trigger conformational changes of the protein, soaking can be misleading and underestimates the number of possible polar interactions due to inadequate, highly impaired positions of protein amino-acid side and main chain atoms. Thus, if applicable cocrystallization should be the gold standard to study protein-ligand complexes.
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