Entropy-Enthalpy Compensation: Role and Ramifications in Biomolecular Ligand Recognition and Design
Open accessAbstract
Recent calorimetric studies of interactions between small molecules and biomolecular targets have generated renewed interest in the phenomenon of entropy-enthalpy compensation. In these studies, entropic and enthalpic contributions to binding are observed to vary substantially and in an opposing manner as the ligand or protein is modified, whereas the binding free energy varies little. In severe examples, engineered enthalpic gains can lead to completely compensating entropic penalties, frustrating ligand design. Here, we examine the evidence for compensation, as well as its potential origins, prevalence, severity, and ramifications for ligand engineering. We find the evidence for severe compensation to be weak in light of the large magnitude of and correlation between errors in experimental measurements of entropic and enthalpic contributions to binding, though a limited form of compensation may be common. Given the difficulty of predicting or measuring entropic and enthalpic changes to useful precision, or using this information in design, we recommend ligand engineering efforts instead focus on computational and experimental methodologies to directly assess changes in binding free energy.
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While the path-based PMF approach appears more tractable, it is still difficult to obtain converged free energy estimates for large biomolecules with complex geometries.
“While the path-based PMF approach appears more tractable, it is still difficult to obtain converged free energy estimates for large biomolecules with complex geometries.53,62−68”
From Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints (2025) · cites this paper as [66]
In “Designing for improvements in affinity directly is likely to be more productive” (page unavailable), the paper describes calculating binding free energies along an unbinding pathway and says slow protein conformational changes remain a challenge. It does not specifically say that path-based PMF estimates fail to converge for large biomolecules with complex geometries, or compare the tractability of that approach with others. (LLM, conf=0.80)
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Cites
Hou, T., Wang, J., Li, Y., & Wang, W. (2010) · Journal of Chemical Information and Modeling · doi:10.1021/ci100275a · Cited by 2,800 · see citing works
Rapid measurement of binding constants and heats of binding using a new titration calorimeter
Wiseman, T., Williston, S., Brandts, J. F., & Lin, L. (1989) · Analytical Biochemistry · doi:10.1016/0003-2697(89)90213-3 · Cited by 2,677 · see citing works
BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities
Liu, T., Lin, Y., Wen, X., Jorissen, R. N., & Gilson, M. K. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl999 · Cited by 2,145 · see citing works
Virtual screening of chemical libraries
Shoichet, B. K. (2004) · Nature · doi:10.1038/nature03197 · Cited by 1,425 · see citing works
Lumry, R. W., & Rajender, S. (1970) · Biopolymers · doi:10.1002/bip.1970.360091002 · Cited by 1,224 · see citing works
The statistical-thermodynamic basis for computation of binding affinities: a critical review
Gilson, M. K., Given, J. A., Bush, B. L., & McCammon, J. A. (1997) · Biophysical Journal · doi:10.1016/s0006-3495(97)78756-3 · Cited by 1,222 · see citing works
New approach to Monte Carlo calculation of the free energy: Method of expanded ensembles
Lyubartsev, A. P., Martsinovski, A. A., Шевкунов, С. В., & Vorontsov‐Velyaminov, P. N. (1992) · The Journal of Chemical Physics · doi:10.1063/1.462133 · Cited by 1,026 · see citing works
The maximal affinity of ligands
Kuntz, I. D., Chen, K., Sharp, K. A., & Kollman, P. A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.9997 · Cited by 859 · see citing works
Converging free energy estimates: MM‐PB(GB)SA studies on the protein–protein complex Ras–Raf
Gohlke, H., & Case, D. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.10379 · Cited by 836 · see citing works
INHIBITORS OF HIV-1 PROTEASE: A Major Success of Structure-Assisted Drug Design
Wlodawer, A., & Vondrasek, J. (1998) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.27.1.249 · Cited by 734 · see citing works
THE ENTHALPY-ENTROPY RELATIONSHIP AND ITS IMPLICATIONS FOR ORGANIC CHEMISTRY
Leffler, J. E. (1955) · The Journal of Organic Chemistry · doi:10.1021/jo01126a009 · Cited by 711 · see citing works
Win some, lose some: enthalpy-entropy compensation in weak intermolecular interactions
Dunitz, J. D. (1995) · Chemistry & Biology · doi:10.1016/1074-5521(95)90097-7 · Cited by 669 · see citing works
Calculation of absolute protein–ligand binding free energy from computer simulations
Woo, H.-J., & Roux, B. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409005102 · Cited by 661 · see citing works
Rekharsky, M. V., Mori, T., Yang, C., Ko, Y. H., Selvapalam, N., Kim, H., Sobransingh, D., Kaifer, A. E., Liu, S., Isaacs, L., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706407105 · Cited by 583 · see citing works
Absolute Binding Free Energies: A Quantitative Approach for Their Calculation
Boresch, S., Tettinger, F., Leitgeb, M., & Karplus, M. (2003) · The Journal of Physical Chemistry B · doi:10.1021/jp0217839 · Cited by 569 · see citing works
Alchemical free energy methods for drug discovery: Progress and challenges
Chodera, J., Mobley, D., Shirts, M., Dixon, R. W., Branson, K., & Pande, V. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.01.011 · Cited by 545 · see citing works
Self-citationComputations of Standard Binding Free Energies with Molecular Dynamics Simulations
Deng, Y., & Roux, B. (2009) · Journal of Physical Chemistry B · doi:10.1021/jp807701h · Cited by 545 · see citing works
Protein activity regulation by conformational entropy
Tzeng, S.-R., & Kalodimos, C. G. (2012) · Nature · doi:10.1038/nature11271 · Cited by 545 · see citing works
Virtual screening: an endless staircase?
Schneider, G. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3139 · Cited by 536 · see citing works
Swanson, J. M. J., Henchman, R. H., & McCammon, J. A. (2004) · Biophysical Journal · doi:10.1016/s0006-3495(04)74084-9 · Cited by 522 · see citing works
Do enthalpy and entropy distinguish first in class from best in class?
Freire, E. (2008) · Drug Discovery Today · doi:10.1016/j.drudis.2008.07.005 · Cited by 491 · see citing works
Tembre, B. L., & McCammon, J. A. (1984) · Computers & Chemistry · doi:10.1016/0097-8485(84)85020-2 · Cited by 459 · see citing works
Recognizing Pitfalls in Virtual Screening: A Critical Review
Scior, T., Bender, A., Tresadern, G., Medina-Franco, J. L., Martínez-Mayorga, K., Langer, T., Cuanalo-Contreras, K., & Agrafiotis, D. K. (2012) · Journal of Chemical Information and Modeling · doi:10.1021/ci200528d · Cited by 438 · see citing works
Entropy—enthalpy compensation: Fact or artifact?
Sharp, K. A. (2001) · Protein Science · doi:10.1110/ps.37801 · Cited by 426 · see citing works
Standard thermodynamics of transfer. Uses and misuses
Ben-Naim, A. Y. (1978) · The Journal of Physical Chemistry · doi:10.1021/j100496a008 · Cited by 420 · see citing works
Adding calorimetric data to decision making in lead discovery: a hot tip
Ladbury, J., Klebe, G., & Freire, E. (2010) · Nature reviews. Drug discovery · doi:10.1038/nrd3054 · Cited by 401 · see citing works
Theory of Free Energy and Entropy in Noncovalent Binding
Zhou, H., & Gilson, M. K. (2009) · Chemical Reviews · doi:10.1021/cr800551w · Cited by 386 · see citing works
Solvent Reorganization and Thermodynamic Enthalpy-Entropy Compensation
Grunwald, E., & Steel, C. (1995) · Journal of the American Chemical Society · doi:10.1021/ja00126a009 · Cited by 373 · see citing works
Snyder, P. W., Mecinović, J., Moustakas, D. T., Thomas, S. W., Harder, M., Mack, E. T., Lockett, M. R., Heroux, A., Sherman, W., & Whitesides, G. M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114107108 · Cited by 358 · see citing works
Isothermal titration calorimetry to determine association constants for high-affinity ligands
Velázquez‐Campoy, A., & Freire, E. (2006) · Nature Protocols · doi:10.1038/nprot.2006.28 · Cited by 347 · see citing works
Hess, B., & van der Vegt, N. F. A. (2006) · The Journal of Physical Chemistry B · doi:10.1021/jp0641029 · Cited by 333 · see citing works
Cooper, A., Johnson, C. M., Lakey, J. H., & Nöllmann, M. (2001) · Biophysical Chemistry · doi:10.1016/s0301-4622(01)00222-8 · Cited by 330 · see citing works
Böhm, H., & Klebe, G. (1996) · Angewandte Chemie International Edition in English · doi:10.1002/anie.199625881 · Cited by 328 · see citing works
Predicting Absolute Ligand Binding Free Energies to a Simple Model Site
Mobley, D. L., Graves, A. P., Chodera, J. D., McReynolds, A. C., Shoichet, B. K., & Dill, K. A. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.06.002 · Cited by 310 · see citing works
Self-citationSolvent reorganization contribution to the transfer thermodynamics of small nonpolar molecules
Lee, B. (1991) · Biopolymers · doi:10.1002/bip.360310809 · Cited by 257 · see citing works
Molecular driving forces : statistical thermodynamics in chemistry and biology
Dill, K. A., Bromberg, S., & Stigter, D. (2003) · Cited by 254 · see citing works
Enthalpy—entropy compensation: a phantom phenomenon
Cornish-Bowden, A. J. (2002) · Journal of Biosciences · doi:10.1007/bf02703768 · Cited by 248 · see citing works
Isothermal Titration Calorimetry
Velázquez‐Campoy, A., Ohtaka, H., Nezami, A., Muzammil, S., & Freire, E. (2004) · Current Protocols in Cell Biology · doi:10.1002/0471143030.cb1708s23 · Cited by 243 · see citing works
Molecular Driving Forces: Statistical Thermodynamics in Chemistry and Biology
Lapedes, A. S. (2003) · Briefings in Bioinformatics · doi:10.1093/bib/4.4.382 · Cited by 242 · see citing works
Martin, Y. C. (2009) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-009-9303-2 · Cited by 237 · see citing works
How Can Hydrophobic Association Be Enthalpy Driven?
Setny, P., Baron, R., & McCammon, J. A. (2010) · Journal of Chemical Theory and Computation · doi:10.1021/ct1003077 · Cited by 234 · see citing works
The Experimental Uncertainty of Heterogeneous Public Ki Data
Krämer, C., Kalliokoski, T., Gedeck, P., & Vulpetti, A. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm300131x · Cited by 234 · see citing works
Holloway, M. K., Wai, J., Halgren, T. A., Fitzgerald, P. M. D., Vacca, J. P., Dorsey, B. D., Levin, R. B., Thompson, W. J., & Chen, L. J. (1995) · Journal of Medicinal Chemistry · doi:10.1021/jm00002a012 · Cited by 232 · see citing works
Concerning the Isokinetic Relationship
Exner, O. (1964) · Nature · doi:10.1038/201488b0 · Cited by 214 · see citing works
Chang, C. A., & Gilson, M. K. (2004) · Journal of the American Chemical Society · doi:10.1021/ja047115d · Cited by 212 · see citing works
Enthalpy−Entropy Compensation: A Phantom or Something Useful?
STARIKOV, E. B., & Nordén, B. (2007) · The Journal of Physical Chemistry B · doi:10.1021/jp075784i · Cited by 207 · see citing works
Statistical interpretation of enthalpy–entropy compensation
Krug, R. R., Hunter, W. G., & Grieger, R. A. (1976) · Nature · doi:10.1038/261566a0 · Cited by 200 · see citing works
Compensating Enthalpic and Entropic Changes Hinder Binding Affinity Optimization
Lafont, V., Armstrong, A. A., Ohtaka, H., Kiso, Y., Amzel, L. M., & Freire, E. (2007) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2007.00519.x · Cited by 195 · see citing works
Coarse-graining entropy, forces, and structures
Rudzinski, J. F., & Noid, W. G. (2011) · The Journal of Chemical Physics · doi:10.1063/1.3663709 · Cited by 187 · see citing works
Direct calculation of the binding free energies of FKBP ligands
Fujitani, H., Tanida, Y., Ito, M., Jayachandran, G., Snow, C. D., Shirts, M. R., Sorin, E. J., & Pande, V. S. (2005) · The Journal of Chemical Physics · doi:10.1063/1.1999637 · Cited by 187 · see citing works
Enthalpy-entropy compensation analysis of pharmaceutical, biochemical and biological systems
Tomlinson, E. (1983) · International Journal of Pharmaceutics · doi:10.1016/0378-5173(83)90001-7 · Cited by 184 · see citing works
Rescoring docking hit lists for model cavity sites: predictions and experimental testing.
Graves, A. P., Shivakumar, D., Boyce, S. E., Jacobson, M., Case, D., & Shoichet, B. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.01.049 · Cited by 184 · see citing works
Predicting ligand binding affinity with alchemical free energy methods in a polar model binding site
Boyce, S. E., Mobley, D., Rocklin, G., Graves, A. P., Dill, K., & Shoichet, B. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.09.049 · Cited by 180 · see citing works
Self-citationA Two-State Model of Hydrophobic Hydration That Produces Compensating Enthalpy and Entropy Changes
Lee, B., & Graziano, G. (1996) · Journal of the American Chemical Society · doi:10.1021/ja9538389 · Cited by 180 · see citing works
Extent of enthalpy–entropy compensation in protein–ligand interactions
Olsson, T. S. G., Ladbury, J. E., Pitt, W. R., & Williams, M. A. (2011) · Protein Science · doi:10.1002/pro.692 · Cited by 171 · see citing works
Thermodynamics of Ligand Binding and Efficiency
Reynolds, C. H., & Holloway, M. K. (2011) · ACS Medicinal Chemistry Letters · doi:10.1021/ml200010k · Cited by 159 · see citing works
Baum, B., Muley, L., Smolinski, M., Heine, A., Hangauer, D., & Klebe, G. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.02.007 · Cited by 157 · see citing works
Searle, M. S., Westwell, M. S., & Williams, D. H. (1995) · Journal of the Chemical Society Perkin Transactions 2 · doi:10.1039/p29950000141 · Cited by 143 · see citing works
Entropy−Enthalpy Compensation in Solvation and Ligand Binding Revisited
Gallicchio, E., Kubo, M. M., & Levy, R. M. (1998) · Journal of the American Chemical Society · doi:10.1021/ja974061h · Cited by 136 · see citing works
Thermodynamics guided lead discovery and optimization
Ferenczy, G. G., & Keserű, G. M. (2010) · Drug Discovery Today · doi:10.1016/j.drudis.2010.08.013 · Cited by 135 · see citing works
Entropy-enthalpy compensation: Perturbation and relaxation in thermodynamic systems
Qian, H., & Hopfield, J. J. (1996) · The Journal of Chemical Physics · doi:10.1063/1.472728 · Cited by 132 · see citing works
Isothermal titration calorimetry at very low c
Tellinghuisen, J. (2007) · Analytical Biochemistry · doi:10.1016/j.ab.2007.08.039 · Cited by 123 · see citing works
Fenley, A. T., Muddana, H. S., & Gilson, M. (2012) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1213180109 · Cited by 122 · see citing works
Petersen, R. C., Markgraf, J. H., & Ross, S. D. (1961) · Journal of the American Chemical Society · doi:10.1021/ja01479a021 · Cited by 122 · see citing works
Hydration effects in protein unfolding
Makhatadze, G. I., & Privalov, P. L. (1994) · Biophysical Chemistry · doi:10.1016/0301-4622(94)00050-6 · Cited by 117 · see citing works
Enthalpy−Entropy Compensation is Not a General Feature of Weak Association
Ford, D. M. (2005) · Journal of the American Chemical Society · doi:10.1021/ja054519c · Cited by 113 · see citing works
The Linear Relationship between Enthalpy and Entropy of Activation
Petersen, R. C. (1964) · The Journal of Organic Chemistry · doi:10.1021/jo01034a001 · Cited by 113 · see citing works
Christensen, T., Gooden, D. M., Kung, J. E., & Toone, E. J. (2003) · Journal of the American Chemical Society · doi:10.1021/ja021240c · Cited by 110 · see citing works
Talhout, R., Villa, A., Mark, A. E., & Engberts, J. B. F. N. (2003) · Journal of the American Chemical Society · doi:10.1021/ja034676g · Cited by 109 · see citing works
Ferrari, A. M., Degliesposti, G., Sgobba, M., & Rastelli, G. (2007) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2007.08.019 · Cited by 105 · see citing works
Myszka, D. G., Abdiche, Y. N., Arisaka, F., Byron, O., Eisenstein, E., Hensley, P., Thomson, J. A., Lombardo, C. R., Schwarz, F., Stafford, W. F., et al. (2003) · PubMed Central · Cited by 103 · see citing works
Advances in all atom sampling methods for modeling protein–ligand binding affinities
Gallicchio, E., & Levy, R. M. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.01.010 · Cited by 101 · see citing works
Multi-Site λ-dynamics for simulated Structure-Activity Relationship studies
Knight, J. L., & Brooks, C. (2011) · Journal of Chemical Theory and Computation · doi:10.1021/ct200444f · Cited by 98 · see citing works
Titration Calorimetry Standards and the Precision of Isothermal Titration Calorimetry Data
Baranauskienė, L., Petrikaitė, V., Matulienė, J., & Matulis, D. (2009) · International Journal of Molecular Sciences · doi:10.3390/ijms10062752 · Cited by 98 · see citing works
Christ, C. D., & van Gunsteren, W. V. (2008) · Journal of Chemical Physics · doi:10.1063/1.2913050 · Cited by 96 · see citing works
Zeevaart, J. G., Wang, L., Thakur, V. V., Leung, C. S., Tirado‐Rives, J., Bailey, C. M., Domaoal, R. A., Anderson, K. S., & Jorgensen, W. L. (2008) · Journal of the American Chemical Society · doi:10.1021/ja8019214 · Cited by 93 · see citing works
Optimizing Experimental Parameters in Isothermal Titration Calorimetry
Tellinghuisen, J. (2005) · The Journal of Physical Chemistry B · doi:10.1021/jp053550y · Cited by 93 · see citing works
The fundamental role of flexibility on the strength of molecular binding
Forrey, C., Douglas, J. F., & Gilson, M. K. (2012) · Soft Matter · doi:10.1039/c2sm25160d · Cited by 92 · see citing works
Heat capacity changes for protein-peptide interactions in the ribonuclease S system
Varadarajan, R., Connelly, P. R., Sturtevant, J. M., & Richards, F. M. (1992) · Biochemistry · doi:10.1021/bi00120a019 · Cited by 92 · see citing works
Van't Hoff analysis of K°(T): How good…or bad?
Tellinghuisen, J. (2005) · Biophysical Chemistry · doi:10.1016/j.bpc.2005.10.012 · Cited by 91 · see citing works
DeLorbe, J. E., Clements, J. H., Whiddon, B. B., & Martin, S. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml100142y · Cited by 88 · see citing works
Extreme Entropy–Enthalpy Compensation in a Drug-Resistant Variant of HIV-1 Protease
King, N. M., Prabu-Jeyabalan, M., Bandaranayake, R. M., Nalam, M. N. L., Nalivaika, E. A., Özen, A., Haliloǧlu, T., Yılmaz, N. K., & Schiffer, C. A. (2012) · ACS Chemical Biology · doi:10.1021/cb300191k · Cited by 88 · see citing works
The role of backlash in the “first injection anomaly” in isothermal titration calorimetry
Mizoue, L. S., & Tellinghuisen, J. (2004) · Analytical Biochemistry · doi:10.1016/j.ab.2003.10.048 · Cited by 87 · see citing works
Let’s get honest about sampling
Mobley, D. (2011) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-011-9497-y · Cited by 83 · see citing works
Self-citationHansen, L. D., Fellingham, G. W., & Russell, D. J. (2010) · Analytical Biochemistry · doi:10.1016/j.ab.2010.11.002 · Cited by 82 · see citing works
Systematic errors in isothermal titration calorimetry: Concentrations and baselines
Tellinghuisen, J., & Chodera, J. D. (2011) · Analytical Biochemistry · doi:10.1016/j.ab.2011.03.024 · Cited by 81 · see citing works
Self-citationEntropy–enthalpy compensation and anticompensation: solvation and ligand binding
Exner, O. (2000) · Chemical Communications · doi:10.1039/b002758h · Cited by 73 · see citing works
STARIKOV, E. B., & Nordén, B. (2012) · Chemical Physics Letters · doi:10.1016/j.cplett.2012.04.028 · Cited by 70 · see citing works
A Note on the Standard State’s Binding Free Energy
General, I. J. (2010) · Journal of Chemical Theory and Computation · doi:10.1021/ct100255z · Cited by 68 · see citing works
A comprehensive examination of the contributions to the binding entropy of protein–ligand complexes
Singh, N., & Warshel, A. (2010) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22689 · Cited by 67 · see citing works
Enthalpic Efficiency of Ligand Binding
Ferenczy, G. G., & Keserű, G. M. (2010) · Journal of Chemical Information and Modeling · doi:10.1021/ci100125a · Cited by 64 · see citing works
A study of statistical error in isothermal titration calorimetry
Tellinghuisen, J. (2003) · Analytical Biochemistry · doi:10.1016/s0003-2697(03)00406-8 · Cited by 64 · see citing works
Tellinghuisen, J. (2005) · Analytical Biochemistry · doi:10.1016/j.ab.2005.04.026 · Cited by 56 · see citing works
Baron, R., & Molinero, V. (2012) · Journal of Chemical Theory and Computation · doi:10.1021/ct300121r · Cited by 53 · see citing works
Brandt, T., Holzmann, N., Muley, L., Khayat, M. T. A., Gerlach, C., Baum, B., Heine, A., Hangauer, D. G., & Klebe, G. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.11.038 · Cited by 53 · see citing works
Tellinghuisen, J. (2012) · Analytical Biochemistry · doi:10.1016/j.ab.2011.12.035 · Cited by 52 · see citing works
Kuroki, R., Nitta, K., & Yutani, K. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35764-8 · Cited by 49 · see citing works
Best practices in free energy calculations for drug design.
Shirts, M. (2012) · Methods in molecular biology · doi:10.1007/978-1-61779-465-0_26 · Cited by 48 · see citing works
Ferrante, A., & Gorski, J. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2012.01.057 · Cited by 47 · see citing works
Exner, O. (1997) · Journal of Physical Organic Chemistry · doi:10.1002/(sici)1099-1395(199711)10:11 · Cited by 44 · see citing works
Ward, J. M., Gorenstein, N., Tian, J., Martin, S. F., & Post, C. B. (2010) · Journal of the American Chemical Society · doi:10.1021/ja910535j · Cited by 43 · see citing works
Entropy-enthalpy compensation: Conformational fluctuation and induced-fit
Qian, H. (1998) · The Journal of Chemical Physics · doi:10.1063/1.477669 · Cited by 41 · see citing works
Optimizing Experimental Parameters in Isothermal Titration Calorimetry: Variable Volume Procedures
Tellinghuisen, J. (2007) · The Journal of Physical Chemistry B · doi:10.1021/jp074515p · Cited by 40 · see citing works
Statistical Error in Isothermal Titration Calorimetry
Tellinghuisen, J. (2004) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(04)83011-8 · Cited by 38 · see citing works
Recent Developments in Isothermal Titration Calorimetry Label Free Screening
Peters, W. B., Frasca, V., & Brown, R. K. J. (2009) · Combinatorial Chemistry & High Throughput Screening · doi:10.2174/138620709789104889 · Cited by 36 · see citing works
Volume errors in isothermal titration calorimetry
Tellinghuisen, J. (2004) · Analytical Biochemistry · doi:10.1016/j.ab.2004.05.061 · Cited by 34 · see citing works
von Koch, C. S., Heine, A., & Klebe, G. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.11.058 · Cited by 23 · see citing works
Cooper, A. (2011) · Journal of Thermal Analysis and Calorimetry · doi:10.1007/s10973-011-1285-3 · Cited by 21 · see citing works
Molecular driving forces of the pocket–ligand hydrophobic association
Graziano, G. (2012) · Chemical Physics Letters · doi:10.1016/j.cplett.2012.03.020 · Cited by 20 · see citing works
Searching for quantitative entropy‐enthalpy compensation among protein variants
Beasley, J. R., Doyle, D. F., Chen, L., Cohen, D. S., Fine, B. R., & Pielak, G. J. (2002) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.10189 · Cited by 17 · see citing works
On the Enthalpy–Entropy Relationship
Mcgregor, R., & MILIĆEVIĆ, B. (1966) · Nature · doi:10.1038/211523b0 · Cited by 15 · see citing works
An Asymptotic Comparative Analysis of the Thermodynamics of Non-Covalent Association
Qian, H. (2005) · Journal of Mathematical Biology · doi:10.1007/s00285-005-0353-3 · Cited by 12 · see citing works
Designing Ligands to Bind Tightly to Proteins
Whitesides, G. M., Snyder, P. W., Moustakas, D. T., & Mirica, K. A. (2008) · IMPERIAL COLLEGE PRESS eBooks · doi:10.1142/9781848162013_0009 · Cited by 12 · see citing works
Baseline changes in an isothermal titration microcalorimeter
de Rivera, M. R., & Socorro, F. (2005) · Journal of Thermal Analysis and Calorimetry · doi:10.1007/s10973-005-0727-1 · Cited by 12 · see citing works
Structural consequences of an amino acid deletion in the B1 domain of protein G
O’Neil, K. T., Bach, A., & DeGrado, W. F. (2000) · Proteins Structure Function and Bioinformatics · doi:10.1002/1097-0134(20001115)41:3 · Cited by 11 · see citing works
Inclusion of ionization states of ligands in affinity calculations
Donnini, S., Villa, A., Groenhof, G., Mark, A. E., Wierenga, R. K., & Juffer, A. H. (2008) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22326 · Cited by 11 · see citing works
Detecting “Silent” Allosteric Coupling
Fisher, H. F. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-334-9_5 · Cited by 11 · see citing works
On the validity of popular assumptions in computational drug design
Klebe, G. (2011) · Journal of Cheminformatics · doi:10.1186/1758-2946-3-s1-o18 · Cited by 10 · see citing works
Effect of a stirring process in an isothermal titration microcalorimeter
Socorro, F., Nuez, I., Álvarez, L., & de Rivera, M. R. (2004) · Thermochimica Acta · doi:10.1016/j.tca.2003.10.030 · Cited by 4 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- [9]Delorbe JE Clements JH Whiddon BB Martin SF Thermodynamic and Structural Effects of Macrocyclic Constraints in Protein-Ligand Interactions ACS Med. Chem. Lett 2010 1 448 452 21116482 PMC2992351
- [67]Starikov EB Nordén B EnthalpyâĹŠEntropy Compensation: A Phantom or Something Useful? J Phys Chem B 2007 111 14431 14435 18044870
- [113]Jorgensen WL Merz KM Ringe D Reynolds CH Progress and issues for computationally guided lead discovery and optimization Drug Design: Structure- and Ligand-Based Approaches 2009 Cambridge University Press
- [115]Knight JL Brooks CL III Multisite λ Dynamics for Simulated Structure–Activity Relationship Studies J Chem Theory Comput 2011 7 2728 2739 22125476 PMC3223982
- [117]Pitera JW Kollman PA Exhaustive mutagenesis in silico: Multicoordinate free energy calculations on proteins and peptides Proteins 2000 41 385 397 11025549
Cited by
Sorted by citations
Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods
Du, X., Li, Y., Xia, Y.-L., Ai, S.-M., Liang, J., Sang, P., Ji, X., & Liu, S.-Q. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020144 · Cited by 1,669 · see citing works
Regulation of protein-ligand binding affinity by hydrogen bond pairing
Chen, D., Oezguen, N., Urvil, P., Ferguson, C. G., Dann, S. M., & Savidge, T. (2016) · Science Advances · doi:10.1126/sciadv.1501240 · Cited by 937 · see citing works
Molecular Recognition in Chemical and Biological Systems
Persch, E., Dumele∞, O., & Diederich, F. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201408487 · Cited by 659 · see citing works
The aqueous supramolecular chemistry of cucurbit[n]urils, pillar[n]arenes and deep-cavity cavitands
Murray, J. K., Jr., Kim, K., Ogoshi, T., Yao, W., & Gibb, B. C. (2017) · Chemical Society Reviews · doi:10.1039/c7cs00095b · Cited by 619 · see citing works
Experimental Binding Energies in Supramolecular Complexes
Biedermann, F., & Schneider, H. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00583 · Cited by 558 · see citing works
Fu, J., & Schlenoff, J. B. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.5b11878 · Cited by 494 · see citing works
Biophysics in drug discovery: impact, challenges and opportunities
Renaud, J., Chung, C., Danielson, U. H., Egner, U., Hennig, M., Hubbard, R. E., & Nar, H. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.123 · Cited by 388 · see citing works
Water Networks Contribute to Enthalpy/Entropy Compensation in Protein–Ligand Binding
Breiten, B., Lockett, M. R., Sherman, W., Fujita, S., Al-Sayah, M. H., Lange, H., Bowers, C. M., Heroux, A., Krilov, G., & Whitesides, G. M. (2013) · Journal of the American Chemical Society · doi:10.1021/ja4075776 · Cited by 341 · see citing works
Accurate calculation of the absolute free energy of binding for drug molecules
Aldeghi, M., Heifetz, A., Bodkin, M. J., Knapp, S., & Biggin, P. C. (2016) · Chemical Science · doi:10.1039/c5sc02678d · Cited by 347 · see citing works
Ligand-Binding Affinity Estimates Supported by Quantum-Mechanical Methods
Ryde, U., & Söderhjelm, P. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00630 · Cited by 301 · see citing works
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Klebe, G. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4486 · Cited by 298 · see citing works
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Senske, M., Törk, L., Born, B., Havenith, M., Herrmann, C., & Ebbinghaus, S. (2014) · Journal of the American Chemical Society · doi:10.1021/ja503205y · Cited by 285 · see citing works
Meanwell, N. A. (2016) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.6b00043 · Cited by 244 · see citing works
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Siddiqui, K. S. (2016) · Critical Reviews in Biotechnology · doi:10.3109/07388551.2016.1144045 · Cited by 208 · see citing works
Yao, H., Ke, H., Zhang, X., Pan, S., Li, M., Yang, L., Schreckenbach, G., & Jiang, W. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b09157 · Cited by 195 · see citing works
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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
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Ryde, U. (2014) · MedChemComm · doi:10.1039/c4md00057a · Cited by 151 · see citing works
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Bhati, A. P., Wan, S., Wright, D. W., & Coveney, P. V. (2016) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.6b00979 · Cited by 140 · see citing works
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Ritt, C. L., Liu, M., Pham, T. A., Epsztein, R., Kulik, H. J., & Elimelech, M. (2022) · Science Advances · doi:10.1126/sciadv.abl5771 · Cited by 137 · see citing works
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Achazi, K., Haag, R., Ballauff, M., Dernedde, J., Kizhakkedathu, J. N., Maysinger, D., & Multhaup, G. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202006457 · Cited by 121 · see citing works
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Wan, S., Sinclair, R. C., & Coveney, P. V. (2021) · Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences · doi:10.1098/rsta.2020.0082 · Cited by 111 · see citing works
Shefer, I., Lopez, K. P., Straub, A. P., & Epsztein, R. (2022) · Environmental Science & Technology · doi:10.1021/acs.est.2c00912 · Cited by 110 · see citing works
Application of isothermal titration calorimetry as a tool to study natural product interactions
Callies, O., & Daranas, A. H. (2016) · Natural Product Reports · doi:10.1039/c5np00094g · Cited by 109 · see citing works
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Heller, G. T., Sormanni, P., & Vendruscolo, M. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.07.004 · Cited by 104 · see citing works
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Henriksen, N. M., Fenley, A. T., & Gilson, M. (2015) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.5b00405 · Cited by 108 · see citing works
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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
Kabiri, M., & Unsworth, L. D. (2014) · Biomacromolecules · doi:10.1021/bm5004515 · Cited by 105 · see citing works
Fenley, A. T., Henriksen, N. M., Muddana, H. S., & Gilson, M. (2014) · Journal of Chemical Theory and Computation · doi:10.1021/ct5004109 · Cited by 91 · see citing works
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Alster, C. J., von Fischer, J. C., Allison, S., & Treseder, K. K. (2020) · Global Change Biology · doi:10.1111/gcb.15053 · Cited by 96 · see citing works
Kiyoshi, M., Caaveiro, J. M. M., Miura, E., Nagatoishi, S., Nakakido, M., Soga, S., Shirai, H., Kawabata, S., & Tsumoto, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087099 · Cited by 96 · see citing works
Gupta, P., Mohammad, T., Κhan, P., Alajmi, M. F., Hussain, A., Rehman, M. T., & Hassan, M. I. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109245 · Cited by 94 · see citing works
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Pandit, S., & De, M. (2016) · The Journal of Physical Chemistry C · doi:10.1021/acs.jpcc.6b11571 · Cited by 93 · see citing works
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Claveria‐Gimeno, R., Vega, S., Abián, O., & Velázquez‐Campoy, A. (2017) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2017.1297418 · Cited by 93 · see citing works
Wickstrom, L., He, P., Gallicchio, E., & Levy, R. M. (2013) · Journal of Chemical Theory and Computation · doi:10.1021/ct400003r · Cited by 92 · see citing works
Hahn, D. F., Bayly, C. I., Boby, M. L., Macdonald, H. E. B., Chodera, J. D., Gapsys, V., Mey, A. S. J. S., Mobley, D. L., Pérez‐Benito, L., Schindler, C., et al. (2022) · Living Journal of Computational Molecular Science · doi:10.33011/livecoms.4.1.1497 · Cited by 89 · see citing works
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Haines, B. E., Saito, Y., Segawa, Y., Itami, K., & Musaev, D. G. (2016) · ACS Catalysis · doi:10.1021/acscatal.6b02317 · Cited by 87 · see citing works
Khan, A., Waris, H., Rafique, M., Suleman, M., Mohammad, A., Ali, S. S., Khan, T., Waheed, Y., Liao, C., & Wei, D. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.01.059 · Cited by 87 · see citing works
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Cavalcanti, I. D. L., Júnior, F. H. X., Santos-Magalhães, N. S., & Nogueira, M. C. D. B. L. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.123063 · Cited by 83 · see citing works
Zubrienė, A., Smirnovienė, J., Смирнов, А. В., Morkūnaitė, V., Michailovienė, V., Jachno, J., Juozapaitienė, V., Norvaišas, P., Manakova, E., Gražulis, S., et al. (2015) · Biophysical Chemistry · doi:10.1016/j.bpc.2015.05.009 · Cited by 79 · see citing works
Krimmer, S. G., & Klebe, G. (2015) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-015-9867-y · Cited by 79 · see citing works
Krimmer, S. G., Cramer, J., Betz, M., Fridh, V., Karlsson, R., Heine, A., & Klebe, G. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00998 · Cited by 79 · see citing works
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Arbesú, M., Iruela, G., Fuentes, H., Teixeira, J. M. C., & Pons, M. (2018) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2018.00039 · Cited by 79 · see citing works
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Xu, X., Angioletti‐Uberti, S., Lu, Y. Q., Dzubiella, J., & Ballauff, M. (2018) · Langmuir · doi:10.1021/acs.langmuir.8b01802 · Cited by 78 · see citing works
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Fu, H., Cai, W., Hénin, J., Roux, B., & Chipot, C. (2017) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.7b00791 · Cited by 74 · see citing works
Chai, H., Zhao, C., Wang, S., Quan, M., Yang, L., Ke, H., & Jiang, W. (2020) · CCS Chemistry · doi:10.31635/ccschem.020.202000160 · Cited by 77 · see citing works
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Wan, S., Bhati, A. P., Zasada, S. J., Wall, I. D., Green, D. V. S., Bamborough, P., & Coveney, P. V. (2016) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.6b00794 · Cited by 76 · see citing works
DockStream: a docking wrapper to enhance de novo molecular design
Guo, J., Janet, J. P., Bauer, M. R., Nittinger, E., Giblin, K. A., Papadopoulos, K., Voronov, A., Patronov, A., Engkvist, O., & Margreitter, C. (2021) · Journal of Cheminformatics · doi:10.1186/s13321-021-00563-7 · Cited by 77 · see citing works
Thermophoresis of biological and biocompatible compounds in aqueous solution
Niether, D., & Wiegand, S. (2019) · Journal of Physics Condensed Matter · doi:10.1088/1361-648x/ab421c · Cited by 74 · see citing works
Liu, W., Johnson, A. T., & Smith, B. D. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.7b12991 · Cited by 74 · see citing works
BFEE: A User-Friendly Graphical Interface Facilitating Absolute Binding Free-Energy Calculations
Fu, H., Gumbart, J. C., Chen, H., Shao, X., Cai, W., & Chipot, C. J. (2018) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.7b00695 · Cited by 72 · see citing works
Hagler, A. T. (2018) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-018-0134-x · Cited by 72 · see citing works
Khan, A., Gui, J., Ahmad, W., Haq, I., Shahid, M., Khan, A. A., Shah, A., Khan, A., Ali, L., Anwar, Z., et al. (2021) · RSC Advances · doi:10.1039/d1ra04694b · Cited by 68 · see citing works
Binding affinity estimation from restrained umbrella sampling simulations
Kumar, V. G., Polasa, A., Agrawal, S., Kumar, T. K. S., & Moradi, M. (2022) · Nature Computational Science · doi:10.1038/s43588-022-00389-9 · Cited by 72 · see citing works
Bou‐Abdallah, F., Sprague, S. E., Smith, B. M., & Giffune, T. R. (2016) · The Journal of Chemical Thermodynamics · doi:10.1016/j.jct.2016.08.020 · Cited by 67 · see citing works
Wang, E., Liu, H., Wang, J.-M., Weng, G.-Q., Sun, H.-Y., Wang, Z., Kang, Y., & Hou, T.-J. (2020) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c00024 · Cited by 56 · see citing works
van Zundert, G. C. P., Hudson, B. M., de Oliveira, S. H. P., Keedy, D. A., Fonseca, R., Héliou, A., Suresh, P., Borrelli, K. W., Day, T., Fraser, J. S., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01292 · Cited by 65 · see citing works
Proteins: molecules defined by their trade-offs
Bigman, L. S., & Levy, Y. (2019) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2019.11.005 · Cited by 62 · see citing works
Sowole, M. A., & Konermann, L. (2014) · Analytical Chemistry · doi:10.1021/ac501849n · Cited by 60 · see citing works
Tang, Z., & Chang, C. A. (2017) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.7b00899 · Cited by 60 · see citing works
Schönbeck, C., & Holm, R. (2019) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.9b03393 · Cited by 59 · see citing works
Docking and Ligand Binding Affinity: Uses and Pitfalls
Yunta, M. J. R. (2016) · American Journal of Modeling and Optimization · doi:10.12691/ajmo-4-3-2 · Cited by 59 · see citing works
Engineering nanomolar peptide ligands that differentially modulate EphA2 receptor signaling
Gómez‐Soler, M., Gehring, M. P., Lechtenberg, B. C., Zapata-Mercado, E. A., Hristova, K. A., & Pasquale, E. B. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.008213 · Cited by 59 · see citing works
Conformation–activity relationships of polyketide natural products
Larsen, E. M., Wilson, M. R., & Taylor, R. E. (2015) · Natural Product Reports · doi:10.1039/c5np00014a · Cited by 58 · see citing works
Linkuvienė, V., Zubrienė, A., Manakova, E., Petrauskas, V., Baranauskienė, L., Zakšauskas, A., Смирнов, А. В., Gražulis, S., Ladbury, J. E., & Matulis, D. (2018) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583518000082 · Cited by 58 · see citing works
Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima
Morgunova, E. Y., Yin, Y., Das, P. K., Jolma, A., Zhu, F., Popov, A. N., Xu, Y. C., Nilsson, L., & Taipale, J. (2018) · eLife · doi:10.7554/elife.32963 · Cited by 57 · see citing works
Linkuvienė, V., Krainer, G., Chen, W., & Matulis, D. (2016) · Analytical Biochemistry · doi:10.1016/j.ab.2016.10.005 · Cited by 56 · see citing works
Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B
Santofimia‐Castaño, P., Rizzuti, B., Pey, A. L., Soubeyran, P., Vidal, M., Urrutia, R. A., Iovanna, J., & Neira, J. L. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1619932114 · Cited by 56 · see citing works
Salade, L., Wauthoz, N., Deleu, M., Vermeersch, M., Vriese, C. D., Amighi, K., & Goole, J. (2017) · International Journal of Nanomedicine · doi:10.2147/ijn.s147650 · Cited by 56 · see citing works
Peng, W., Ding, F., Peng, Y.-K., Jiang, Y., & Zhang, L. (2013) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf4039327 · Cited by 55 · see citing works
Kantonen, S. A., Henriksen, N. M., & Gilson, M. K. (2016) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2016.09.002 · Cited by 55 · see citing works
Advances in uncovering the mechanisms of macromolecular conformational entropy
Wankowicz, S. A. M., & Fraser, J. S. (2025) · Nature Chemical Biology · doi:10.1038/s41589-025-01879-3 · Cited by 53 · see citing works
A Refined Model for the TSG-6 Link Module in Complex with Hyaluronan
Higman, V. A., Briggs, D. C., Mahoney, D. J., Blundell, C. D., Sattelle, B. M., Dyer, D. P., Green, D. E., DeAngelis, P. L., Almond, A., Milner, C. M., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.542357 · Cited by 53 · see citing works
Structure–affinity relationship of the cocaine-binding aptamer with quinine derivatives
Slavkovic, S., Altunisik, M., Reinstein, O., & Johnson, P. E. (2015) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2015.02.052 · Cited by 53 · see citing works
Direct methods for computing single‐molecule entropies from molecular simulations
Suárez, D., & Díaz, N. (2014) · Wiley Interdisciplinary Reviews Computational Molecular Science · doi:10.1002/wcms.1195 · Cited by 53 · see citing works
Data quality in drug discovery: the role of analytical performance in ligand binding assays
Wätzig, H., Oltmann‐Norden, I., Steinicke, F., Alhazmi, H. A., Nachbar, M., El‐Hady, D. A., Albishri, H. M., Baumann, K., Exner, T. E., Boeckler, F. M., et al. (2015) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-015-9851-6 · Cited by 53 · see citing works
- Authors
- Chodera, J. D., & Mobley, D. L.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- University of California, Irvine (US)
- Venue
- Annual Review of Biophysics
- Publisher
- Annual Reviews
- Published
- 2013-05-06
- Volume
- 42
- Issue
- 1
- Pages
- 121-142
- ISSN
- 1936-122X (ISSN-L)
- 1936-1238
- PMC
- PMC4124006
- OpenAlex
- W2151022427
- Cited by
- 531
- References
- 119
- Citations by year
- 2026: 43 · 2025: 43 · 2024: 35 · 2023: 42 · 2022: 45 · 2021: 42 · 2020: 35 · 2019: 38 · 2018: 36 · 2017: 46 · 2016: 42 · 2015: 46 · 2014: 30 · 2013: 7 · 2012: 1
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Biophysics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1r15gm096257-01a1)
- National Cancer Institute (P30CA008748)
- National Institute of General Medical Sciences (1R15GM096257-01A1, R15 GM096257)
- Topics
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › thermodynamics and calorimetric analyses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- enthalpy-entropy compensation, binding free energy, ligand design, ligand recognition, protein-ligand interactions, calorimetry, binding thermodynamics, ligand engineering
- MeSH terms
- Calorimetry, Ligands, Protein Binding, Proteins, Thermodynamics, Entropy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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