Water, water, everywhere… It’s time to stop and think.

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Role of Molecular Dynamics and Related Methods in Drug Discovery

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Motifs for molecular recognition exploiting hydrophobic enclosure in protein–ligand binding

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Role of the Active-Site Solvent in the Thermodynamics of Factor Xa Ligand Binding

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Self-consistent description of a metal–water interface by the Kohn–Sham density functional theory and the three-dimensional reference interaction site model

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The Entropic Cost of Bound Water in Crystals and Biomolecules

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Alchemical free energy methods for drug discovery: Progress and challenges

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Just add water! The effect of water on the specificity of protein-ligand binding sites and its potential application to drug design

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Chemical potential of hard-sphere fluids by Monte Carlo methods

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Application and Limitations of X‐ray Crystallographic Data in Structure‐Based Ligand and Drug Design

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Water Networks Contribute to Enthalpy/Entropy Compensation in Protein–Ligand Binding

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Inhomogeneous Fluid Approach to Solvation Thermodynamics. 1. Theory

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Grid inhomogeneous solvation theory: hydration structure and thermodynamics of the miniature receptor cucurbit[7]uril.

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Classification of Water Molecules in Protein Binding Sites

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Water in Cavity−Ligand Recognition

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Three-Dimensional Molecular Theory of Solvation Coupled with Molecular Dynamics in Amber

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Energetics of Displacing Water Molecules from Protein Binding Sites: Consequences for Ligand Optimization

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Prediction of protein–ligand binding affinity by free energy simulations: assumptions, pitfalls and expectations

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A cavity-biased (T, V, μ) Monte Carlo method for the computer simulation of fluids

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How Can Hydrophobic Association Be Enthalpy Driven?

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Ligand binding to protein-binding pockets with wet and dry regions

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SuperStar: A Knowledge-based Approach for Identifying Interaction Sites in Proteins

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Hydration in drug design. 1. Multiple hydrogen-bonding features of water molecules in mediating protein-ligand interactions

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λ‐Dynamics free energy simulation methods

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Prediction of the Water Content in Protein Binding Sites

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Rapid and Accurate Prediction and Scoring of Water Molecules in Protein Binding Sites

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The Development of Replica-Exchange-Based Free-Energy Methods

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New insights from structural biology into the druggability of G protein-coupled receptors

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Predicting conserved water-mediated and polar ligand interactions in proteins using a K-nearest-neighbors genetic algorithm

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Limitations and lessons in the use of X-ray structural information in drug design

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Water, water everywhere — except where it matters?

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A Cavity Corrected 3D-RISM Functional for Accurate Solvation Free Energies

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Thermodynamic analysis of water molecules at the surface of proteins and applications to binding site prediction and characterization

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Thermodynamics of Water in an Enzyme Active Site: Grid-Based Hydration Analysis of Coagulation Factor Xa

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WaterScore: a novel method for distinguishing between bound and displaceable water molecules in the crystal structure of the binding site of protein-ligand complexes

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Contribution of Explicit Solvent Effects to the Binding Affinity of Small‐Molecule Inhibitors in Blood Coagulation Factor Serine Proteases

Abel, R., Salam, N. K., Shelley, J. C., Farid, R., Friesner, R. A., & Sherman, W. (2011) · ChemMedChem · doi:10.1002/cmdc.201000533 · Cited by 127 · see citing works

Understanding Kinase Selectivity Through Energetic Analysis of Binding Site Waters

Robinson, D. D., Sherman, W., & Farid, R. (2010) · ChemMedChem · doi:10.1002/cmdc.200900501 · Cited by 125 · see citing works

Water Sites, Networks, And Free Energies with Grand Canonical Monte Carlo

Ross, G. A., Bodnarchuk, M. S., & Essex, J. W. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b07940 · Cited by 122 · see citing works

Water Network Perturbation in Ligand Binding: Adenosine A2AAntagonists as a Case Study

Bortolato, A., Tehan, B. G., Bodnarchuk, M. S., Essex, J. W., & Mason, J. S. (2013) · Journal of Chemical Information and Modeling · doi:10.1021/ci4001458 · Cited by 119 · see citing works

MOLECULAR BINDING

Hummer, G. (2010) · Nature Chemistry · doi:10.1038/nchem.885 · Cited by 119 · see citing works

High‐energy water sites determine peptide binding affinity and specificity of PDZ domains

Beuming, T., Farid, R., & Sherman, W. (2009) · Protein Science · doi:10.1002/pro.177 · Cited by 116 · see citing works

Ligand Mapping on Protein Surfaces by the 3D-RISM Theory: Toward Computational Fragment-Based Drug Design

Imai, T., Oda, K., Kovalenko, A., Hirata, F., & Kidera, A. (2009) · Journal of the American Chemical Society · doi:10.1021/ja905029t · Cited by 112 · see citing works

Interactions between Hofmeister Anions and the Binding Pocket of a Protein

Fox, J. M., Kang, K., Sherman, W., Heroux, A., Sastry, G. M., Baghbanzadeh, M., Lockett, M. R., & Whitesides, G. M. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b00187 · Cited by 105 · see citing works

Hydration Site Thermodynamics Explain SARs for Triazolylpurines Analogues Binding to the A2A Receptor

Higgs, C. J., Beuming, T., & Sherman, W. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml100008s · Cited by 102 · see citing works

Analysis of Biomolecular Solvation Sites by 3D-RISM Theory

Sindhikara, D., & Hirata, F. (2013) · The Journal of Physical Chemistry B · doi:10.1021/jp4046116 · Cited by 97 · see citing works

Hydration in drug design. 3. Conserved water molecules at the ligand-binding sites of homologous proteins

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Calculation of Local Water Densities in Biological Systems: A Comparison of Molecular Dynamics Simulations and the 3D-RISM-KH Molecular Theory of Solvation

Stumpe, M. C., Blinov, N., Wishart, D. S., Kovalenko, A., & Pande, V. S. (2010) · The Journal of Physical Chemistry B · doi:10.1021/jp102587q · Cited by 90 · see citing works

Effects of Water Placement on Predictions of Binding Affinities for p38α MAP Kinase Inhibitors

Luccarelli, J., Michel, J., Tirado‐Rives, J., & Jorgensen, W. L. (2010) · Journal of Chemical Theory and Computation · doi:10.1021/ct100504h · Cited by 83 · see citing works

Hydration in drug design. 2. Influence of local site surface shape on water binding

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Evaluating Free Energies of Binding and Conservation of Crystallographic Waters Using SZMAP

Bayden, A. S., Moustakas, D. T., Joseph‐McCarthy, D., & Lamb, M. L. (2015) · Journal of Chemical Information and Modeling · doi:10.1021/ci500746d · Cited by 80 · see citing works

New hypotheses about the structure–function of proprotein convertase subtilisin/kexin type 9: Analysis of the epidermal growth factor‐like repeat A docking site using WaterMap

Pearlstein, R. A., Hu, Q., Zhou, J., Yowe, D. L., Levell, J. R., Dale, B., Kaushik, V. K., Daniels, D. S., Hanrahan, S., Sherman, W., et al. (2010) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22767 · Cited by 77 · see citing works

AcquaAlta: A Directional Approach to the Solvation of Ligand–Protein Complexes

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Communication: Accurate hydration free energies at a wide range of temperatures from 3D-RISM

Mišin, M., Fedorov, M. V., & Palmer, D. S. (2015) · The Journal of Chemical Physics · doi:10.1063/1.4914315 · Cited by 74 · see citing works

Rigorous Free Energy Calculations in Structure‐Based Drug Design

Michel, J., Foloppe, N., & Essex, J. (2010) · Molecular Informatics · doi:10.1002/minf.201000051 · Cited by 73 · see citing works

More than a bystander

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Quantifying the Entropy of Binding for Water Molecules in Protein Cavities by Computing Correlations

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Enhanced Configurational Sampling in Binding Free-Energy Calculations

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Novel Inverse Binding Mode of Indirubin Derivatives Yields Improved Selectivity for DYRK Kinases

Myrianthopoulos, V., Kritsanida, M., Gaboriaud‐Kolar, N., Magiatis, P., Ferandin, Y., Durieu, É., Lozach, O., Cappel, D., Soundararajan, M., Filippakopoulos, P., et al. (2012) · ACS Medicinal Chemistry Letters · doi:10.1021/ml300207a · Cited by 68 · see citing works

Simulated Annealing of Chemical Potential: A General Procedure for Locating Bound Waters. Application to the Study of the Differential Hydration Propensities of the Major and Minor Grooves of DNA

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Modelling of solvent positions around polar groups in proteins

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Spirocyclic Sulfamides as β-Secretase 1 (BACE-1) Inhibitors for the Treatment of Alzheimer’s Disease: Utilization of Structure Based Drug Design, WaterMap, and CNS Penetration Studies To Identify Centrally Efficacious Inhibitors

Brodney, M. A., Barreiro, G., Ogilvie, K., Hajós‐Korcsok, É., Murray, J. C., Vajdos, F. F., Ambroise, C., Christoffersen, C. L., Fisher, K. E., Lanyon, L. F., et al. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm3009426 · Cited by 60 · see citing works

Contributions of water transfer energy to protein‐ligand association and dissociation barriers: Watermap analysis of a series of p38α MAP kinase inhibitors

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Strategies to Calculate Water Binding Free Energies in Protein–Ligand Complexes

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The Binding of Benzoarylsulfonamide Ligands to Human Carbonic Anhydrase is Insensitive to Formal Fluorination of the Ligand

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MTS-MD of Biomolecules Steered with 3D-RISM-KH Mean Solvation Forces Accelerated with Generalized Solvation Force Extrapolation

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Modified Anderson Method for Accelerating 3D-RISM Calculations Using Graphics Processing Unit

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A 3D‐RISM/RISM study of the oseltamivir binding efficiency with the wild‐type and resistance‐associated mutant forms of the viral influenza B neuraminidase

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Estimating Translational and Orientational Entropies Using the k-Nearest Neighbors Algorithm

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Optimization of Potent DFG-in Inhibitors of Platelet Derived Growth Factor Receptorβ (PDGF-Rβ) Guided by Water Thermodynamics

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An inhibitor-driven study for enhancing the selectivity of indirubin derivatives towards leishmanial Glycogen Synthase Kinase-3 over leishmanial cdc2-related protein kinase 3

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Analysis of water patterns in protein kinase binding sites

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Binding Affinity via Docking: Fact and Fiction

Pantsar, T., & Poso, A. (2018) · Molecules · doi:10.3390/molecules23081899 · Cited by 787 · see citing works

Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165

Wrobleski, S. T., Moslin, R. M., Lin, S., Zhang, Y., Spergel, S. H., Kempson, J., Tokarski, J. S., Strnad, J., Zupa-Fernandez, A., Cheng, L., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00444 · Cited by 401 · see citing works

Alchemical Binding Free Energy Calculations in AMBER20: Advances and Best Practices for Drug Discovery

Lee, T., Allen, B. K., Giese, T. J., Guo, Z., Li, P., Lin, C. H., McGee, T. D., Pearlman, D. A., Radak, B. K., Tao, Y., et al. (2020) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c00613 · Cited by 379 · see citing works

Empirical scoring functions for structure-based virtual screening: applications, critical aspects, and challenges

Guedes, I. A., Pereira, F. S. S., & Dardenne, L. E. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01089 · Cited by 331 · see citing works

Water in protein hydration and ligand recognition

Maurer, M., & Oostenbrink, C. (2019) · Journal of Molecular Recognition · doi:10.1002/jmr.2810 · Cited by 156 · see citing works

Molecular Docking for Drug Discovery and Development: A Widely Used Approach but Far from Perfect

Wang, G., & Zhu, W. (2016) · Future Medicinal Chemistry · doi:10.4155/fmc-2016-0143 · Cited by 153 · see citing works

Rapid, accurate, precise and reproducible ligand–protein binding free energy prediction

Wan, S., Bhati, A. P., Zasada, S. J., & Coveney, P. V. (2020) · Interface Focus · doi:10.1098/rsfs.2020.0007 · Cited by 152 · see citing works

A Survey of the Role of Nitrile Groups in Protein–Ligand Interactions

Wang, Y. E., Du, Y., & Huang, N. (2018) · Future Medicinal Chemistry · doi:10.4155/fmc-2018-0252 · Cited by 142 · see citing works

Structure-Based Design and Pharmacokinetic Optimization of Covalent Allosteric Inhibitors of the Mutant GTPase KRASG12C

Kettle, J. G., Bagal, S. K., Bickerton, S., Bodnarchuk, M. S., Breed, J., Carbajo, R. J., Cassar, D. J., Chakraborty, A., Cosulich, S. C., Cumming, I. A., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01720 · Cited by 85 · see citing works

Testing inhomogeneous solvation theory in structure-based ligand discovery

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Increasing the bioactive space of peptide macrocycles by thioamide substitution

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Achieving <i>In Vivo</i> Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders

Bellenie, B. R., Cheung, K.-M. J., Varela, A., Pierrat, O. A., Collie, G. W., Box, G. M., Bright, M. D., Gowan, S., Hayes, A., Rodrigues, M. J., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b02076 · Cited by 74 · see citing works

Water regulates the residence time of Benzamidine in Trypsin

Ansari, N., Rizzi, V., & Parrinello, M. (2022) · Nature Communications · doi:10.1038/s41467-022-33104-3 · Cited by 65 · see citing works

The role of water in ligand binding.

Zsidó, B. Z., & Hetényi, C. (2020) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2020.08.002 · Cited by 59 · see citing works

Large-scale analysis of water stability in bromodomain binding pockets with grand canonical Monte Carlo

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Discovery of AZD4625, a Covalent Allosteric Inhibitor of the Mutant GTPase KRASG12C

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Approaches to target tractability assessment – a practical perspective

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Advances in the calculation of binding free energies

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Water molecules at protein–drug interfaces: computational prediction and analysis methods

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Computer-Aided Drug Design: An Overview

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Shedding light on important waters for drug design: simulations versus grid-based methods.

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Solvation Structure and Thermodynamic Mapping (SSTMap): An Open-Source, Flexible Package for the Analysis of Water in Molecular Dynamics Trajectories

Haider, K., Cruz, A., Ramsey, S., Gilson, M. K., & Kurtzman, T. (2017) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.7b00592 · Cited by 57 · see citing works

Computer-Aided Drug Discovery and Design: Recent Advances and Future Prospects

Talevi, A. (2023) · Methods in molecular biology · doi:10.1007/978-1-0716-3441-7_1 · Cited by 58 · see citing works

Identification of Conserved Water Sites in Protein Structures for Drug Design

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Computational chemical biology and drug design: Facilitating protein structure, function, and modulation studies

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Ligand Binding Free Energies with Adaptive Water Networks: Two-Dimensional Grand Canonical Alchemical Perturbations

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Picomolar FKBP inhibitors enabled by a single water-displacing methyl group in bicyclic [4.3.1] aza-amides

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BindingDB Entry 50013003: Drugging the undruggable: a computational chemist's view of KRAS

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BindingDB Entry 50008465: Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165.

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BindingDB Entry 50009311: Structure-Based Design and Pharmacokinetic Optimization of Covalent Allosteric Inhibitors of the Mutant GTPase KRAS

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BindingDB Entry 50017856: Discovery of AZD4625, a Covalent Allosteric Inhibitor of the Mutant GTPase KRAS

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