The role of protonation states in ligand-receptor recognition and binding.
Open accessAbstract
In this review we discuss the role of protonation states in receptor-ligand interactions, providing experimental evidences and computational predictions that complex formation may involve titratable groups with unusual pKa's and that protonation states frequently change from unbound to bound states. These protonation changes result in proton uptake/release, which in turn causes the pH-dependence of the binding. Indeed, experimental data strongly suggest that almost any binding is pH-dependent and to be correctly modeled, the protonation states must be properly assigned prior to and after the binding. One may accurately predict the protonation states when provided with the structures of the unbound proteins and their complex; however, the modeling becomes much more complicated if the bound state has to be predicted in a docking protocol or if the structures of either bound or unbound receptor-ligand are not available. The major challenges that arise in these situations are the coupling between binding and protonation states, and the conformational changes induced by the binding and ionization states of titratable groups. In addition, any assessment of the protonation state, either before or after binding, must refer to the pH of binding, which is frequently unknown. Thus, even if the pKa's of ionizable groups can be correctly assigned for both unbound and bound state, without knowing the experimental pH one cannot assign the corresponding protonation states, and consequently one cannot calculate the resulting proton uptake/release. It is pointed out, that while experimental pH may not be the physiological pH and binding may involve proton uptake/release, there is a tendency that the native receptor-ligand complexes have evolved toward specific either subcellular or tissue characteristic pH at which the proton uptake/release is either minimal or absent.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Correct assignment of protein and ligand protonation/tautomeric states with respect to experimental pH, Asn/Gln/His flips, and defined stereocenters is crucial and requires careful inspection of structures.
“The correct assignment of both protein and ligand protonation/tautomeric states with respect to the experimental pH, Asn/Gln/His flips, and defined stereocenters of the compounds are crucial, requiring a careful inspection of the structures (Kalliokoski et al., 2009; Martin, 2009; Petukh et al., 2013; Sastry et al., 2013).”
From Empirical scoring functions for structure-based virtual screening: applications, critical aspects, and challenges (2018) · cites this paper as Petukh et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 45,260 · see citing works
Soil Science Society of America Journal
Article, S. Y. (2020) · Soil Science Society of America Journal · doi:10.1002/(issn)1435-0661 · Cited by 2,019 · see citing works
The atomic structure of protein-protein recognition sites 1 1Edited by A. R. Fersht
Conte, L. L., Chothia, C., & Janin, J. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.2439 · Cited by 1,967 · see citing works
Reactive oxygen species in living systems: Source, biochemistry, and role in human disease
Halliwell, B. B. (1991) · The American Journal of Medicine · doi:10.1016/0002-9343(91)90279-7 · Cited by 1,811 · see citing works
Microenvironmental pH Is a Key Factor for Exosome Traffic in Tumor Cells
Parolini, I., Federici, C., Raggi, C., Lugini, L., Palleschi, S., Milito, A. D., Coscia, C., Iessi, E., Logozzi, M., Molinari, A., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.041152 · Cited by 1,561 · see citing works
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2005) · Chemical & Engineering News · doi:10.1021/cen-v083n019.p031 · Cited by 1,553 · see citing works
Protein complexes and functional modules in molecular networks
Spirin, V., & Mirny, L. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2032324100 · Cited by 1,468 · see citing works
Shape Complementarity at Protein/Protein Interfaces
Lawrence, M. C., & Colman, P. M. (1993) · Journal of Molecular Biology · doi:10.1006/jmbi.1993.1648 · Cited by 1,219 · see citing works
Shape complementarity at protein–protein interfaces
Norel, R., Lin, S. L., Wolfson, H. J., & Nussinov, R. (1994) · Biopolymers · doi:10.1002/bip.360340711 · Cited by 1,208 · see citing works
Indian Journal of Pharmaceutical Sciences
(2021) · doi:10.36468/pharmaceutical-sciences · Cited by 1,113 · see citing works
Calculation of Protein-Ligand Binding Affinities
Gilson, M. K., & Zhou, H. (2007) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.36.040306.132550 · Cited by 966 · see citing works
Diversity of protein–protein interactions
Nooren, I. M. A., & Thornton, J. (2003) · EMBO Journal · doi:10.1093/emboj/cdg359 · Cited by 942 · see citing works
Recent progress in tumor pH targeting nanotechnology
Lee, E. S., Gao, Z., & Bae, Y. H. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.05.003 · Cited by 866 · see citing works
The structure of protein-protein recognition sites.
Janin, J., & Chothia, C. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)46181-3 · Cited by 824 · see citing works
Molecular Recognition and Docking Algorithms
Brooijmans, N., & Kuntz, I. D. (2003) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.32.110601.142532 · Cited by 789 · see citing works
Structural Mechanisms for Domain Movements in Proteins
Gerstein, M., Lesk, A. M., & Chothia, C. (1994) · Biochemistry · doi:10.1021/bi00188a001 · Cited by 741 · see citing works
Biohydrogen Production as a Function of pH and Substrate Concentration
Ginkel, S. V., Sung, S., & Lay, J. (2001) · Environmental Science & Technology · doi:10.1021/es001979r · Cited by 736 · see citing works
Principles of Protein−Protein Interactions: What are the Preferred Ways For Proteins To Interact?
Keskin, O., Gursoy, A., Ma, B., & Nussinov, R. (2008) · Chemical Reviews · doi:10.1021/cr040409x · Cited by 697 · see citing works
Conformational entropy in molecular recognition by proteins
Frederick, K. K., Marlow, M. S., Valentine, K. G., & Wand, A. J. (2007) · Nature · doi:10.1038/nature05959 · Cited by 663 · see citing works
The RCSB Protein Data Bank: redesigned web site and web services
Rose, P. W., Beran, B., Bi, C., Bluhm, W. F., Dimitropoulos, D., Goodsell, D. S., Prlić, A., Quesada, M., Quinn, G. B., Westbrook, J., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1021 · Cited by 659 · see citing works
Surface, subunit interfaces and interior of oligomeric proteins
Janin, J., Miller, S. M., & Chothia, C. (1988) · Journal of Molecular Biology · doi:10.1016/0022-2836(88)90606-7 · Cited by 653 · see citing works
Analysis of protein-protein interaction sites using surface patches 1 1Edited by G.Von Heijne
Jones, S., & Thornton, J. M. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1234 · Cited by 603 · see citing works
Structural Characterisation and Functional Significance of Transient Protein–Protein Interactions
Nooren, I., & Thornton, J. M. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)01281-0 · Cited by 587 · see citing works
Rapid, electrostatically assisted association of proteins
Schreiber, G., & Fersht, A. R. (1996) · Nature Structural Biology · doi:10.1038/nsb0596-427 · Cited by 560 · see citing works
Antibody-antigen interactions: new structures and new conformational changes
Wilson, I. A., & Stanfield, R. L. (1994) · Current Opinion in Structural Biology · doi:10.1016/0959-440x(94)90267-4 · Cited by 517 · see citing works
Communications in Computational Physics
(2025) · Communications in Computational Physics · doi:10.4208/cicp · Cited by 510 · see citing works
The Relative Effectiveness of pH Control and Heat Treatment for Enhancing Biohydrogen Gas Production
Oh, S., Ginkel, S. V., & Logan, B. E. (2003) · Environmental Science & Technology · doi:10.1021/es034291y · Cited by 493 · see citing works
Soil Redox and pH Effects on Methane Production in a Flooded Rice Soil
Wang, Z. P., DeLaune, R. D., Patrick, W. H., & Masscheleyn, P. H. (1993) · Soil Science Society of America Journal · doi:10.2136/sssaj1993.03615995005700020016x · Cited by 469 · see citing works
Kirchmair, J., Markt, P., Distinto, S., Wolber, G., & Langer, T. (2008) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-007-9163-6 · Cited by 423 · see citing works
Protein–protein interaction and quaternary structure
Janin, J., Bahadur, R. P., & Chakrabarti, P. (2008) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583508004708 · Cited by 400 · see citing works
Igawa, T., Ishii, S., Tachibana, T., Maeda, A., Higuchi, Y., Shimaoka, S., Moriyama, C., Watanabe, T., Takubo, R., Doi, Y., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1691 · Cited by 349 · see citing works
Are protein–protein interfaces more conserved in sequence than the rest of the protein surface?
Caffrey, D. R., Somaroo, S. S., Hughes, J. D., Mintseris, J., & Huang, E. S. (2003) · Protein Science · doi:10.1110/ps.03323604 · Cited by 339 · see citing works
Protein topology determines binding mechanism
Levy, Y., Wolynes, P. G., & Onuchic, J. N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2534828100 · Cited by 324 · see citing works
Venetsaneas, N., Αντωνοπούλου, Γ., Stamatelatou, Κ., Kornaros, M. E., & Lyberatos, G. (2009) · Bioresource Technology · doi:10.1016/j.biortech.2009.01.025 · Cited by 300 · see citing works
A novel mechanism of tumorigenesis involving pH-dependent destabilization of a mutant p53 tetramer
DiGiammarino, E. L., Lee, A. S., Cadwell, C., Zhang, W., Bothner, B. B., Ribeiro, R. C., Zambetti, G. P., & Kriwacki, R. W. (2001) · Nature Structural Biology · doi:10.1038/nsb730 · Cited by 293 · see citing works
Physical Properties of Whey Protein Stabilized Emulsions as Related to pH and NaCl
Demetriades, K., Coupland, J. N., & McClements, D. J. (1997) · Journal of Food Science · doi:10.1111/j.1365-2621.1997.tb03997.x · Cited by 286 · see citing works
Food Microbiology : An Introduction
Montville, T. J., & Matthews, K. R. (2005) · Cited by 284 · see citing works
pH-Dependent partitioning in room temperature ionic liquids
Visser, A. E., Swatloski, R. P., & Rogers, R. D. (2000) · Green Chemistry · doi:10.1039/a908888a · Cited by 281 · see citing works
Guinee, T. P., Feeney, E. P., Auty, M. A. E., & Fox, P. F. (2002) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(02)74238-0 · Cited by 271 · see citing works
Progress in the prediction of p K a values in proteins
Alexov, E. G., Mehler, E. L., Baker, N., Baptista, A. M., Huang, Y. G., Milletti, F., Nielsen, J. E., Farrell, D., Carstensen, T., Olsson, M. H. M., et al. (2011) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.23189 · Cited by 269 · see citing works
Self-citationTransient protein-protein interactions
Acuner, S. E., Engin, H. B., Gürsoy, A., & Keskin, Ö. (2011) · Protein Engineering Design and Selection · doi:10.1093/protein/gzr025 · Cited by 265 · see citing works
On the Role of Electrostatic Interactions in the Design of Protein–Protein Interfaces
Sheinerman, F. B., & Honig, B. H. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00030-x · Cited by 252 · see citing works
Electrostatic complementarity at protein/protein interfaces 1 1Edited by B. Honig
McCoy, A. J., Epa, V. C., & Colman, P. M. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.0987 · Cited by 249 · see citing works
Geisow, M. J., Hart, P. D., & Young, M. R. (1981) · The Journal of Cell Biology · doi:10.1083/jcb.89.3.645 · Cited by 248 · see citing works
Wu, X. L., Kim, J. H., Koo, H., Bae, S. M., Shin, H., Kim, M.-S., Lee, B.-H., Park, R., Kim, I.-S., Choi, K., et al. (2010) · Bioconjugate Chemistry · doi:10.1021/bc9005283 · Cited by 239 · see citing works
Xu, D., Lin, S. L., & Nussinov, R. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0712 · Cited by 231 · see citing works
Morphology of protein–protein interfaces
Larsen, T. A., Olson, A. J., & Goodsell, D. S. (1998) · Structure · doi:10.1016/s0969-2126(98)00044-6 · Cited by 228 · see citing works
Electrostatic Influence on the Kinetics of Ligand Binding to Acetylcholinesterase
Radić, Z., Kirchhoff, P. D., Quinn, D. M., McCammon, J. A., & Taylor, P. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.37.23265 · Cited by 224 · see citing works
Gunner, M. R., Nicholls, A. O., & Honig, B. H. (1996) · The Journal of Physical Chemistry · doi:10.1021/jp9519070 · Cited by 208 · see citing works
Vijayakumar, M., Wong, K.-Y., Schreiber, G., Fersht, A. R., Szabó, A., & Zhou, H. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.1747 · Cited by 199 · see citing works
Room Temperature Ionic Liquids for Separating Organics from Produced Water
McFarlane, J., Ridenour, W. B., Luo, H., et al. (2005) · Separation Science and Technology · doi:10.1081/ss-200052807 · Cited by 194 · see citing works
Hydrophobic docking: A proposed enhancement to molecular recognition techniques
Vakser, I. A., & Aflalo, C. (1994) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340200405 · Cited by 190 · see citing works
Influence of Protonation, Tautomeric, and Stereoisomeric States on Protein−Ligand Docking Results
ten Brink, T., & Exner, T. E. (2009) · Journal of Chemical Information and Modeling · doi:10.1021/ci800420z · Cited by 175 · see citing works
On the role of electrostatics in protein–protein interactions
Zhang, Z., Witham, S., & Alexov, E. G. (2011) · Physical Biology · doi:10.1088/1478-3975/8/3/035001 · Cited by 169 · see citing works
Self-citationExploring the Free Energy Landscape: From Dynamics to Networks and Back
Prada‐Gracia, D., Gómez‐Gardeñes, J., Echenique, P. M., & Falo, F. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000415 · Cited by 168 · see citing works
A Continuum Model for Protein–Protein Interactions: Application to the Docking Problem
Jackson, R. M., & Sternberg, M. J. E. (1995) · Journal of Molecular Biology · doi:10.1006/jmbi.1995.0375 · Cited by 166 · see citing works
Harms, M. J., Castañeda, C. A., Schlessman, J. L., Sue, G. R., Isom, D. G., Cannon, B. R., & Bertrand García‐Moreno, E. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.03.039 · Cited by 156 · see citing works
Electrostatic rate enhancement and transient complex of protein–protein association
Alsallaq, R. A., & Zhou, H. (2007) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21679 · Cited by 153 · see citing works
Introduction to cell and tissue culture: theory and technique
(1999) · Choice Reviews Online · doi:10.5860/choice.36-4476 · Cited by 140 · see citing works
Cozzini, P., Fornabaio, M., Marabotti, A., Abraham, D. J., Kellogg, G. E., & Mozzarelli, A. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm0200299 · Cited by 130 · see citing works
Barstar is electrostatically optimized for tight binding to barnase.
Tidor, B., & Lee, L. (2001) · Nature Structural Biology · doi:10.1038/83082 · Cited by 124 · see citing works
Tautomerism in Computer‐Aided Drug Design
Pospíšil, P., Ballmer, P., Scapozza, L., & Folkers, G. (2003) · Journal of Receptors and Signal Transduction · doi:10.1081/rrs-120026975 · Cited by 122 · see citing works
Automated Prediction of Protein Association Rate Constants
Qin, S., Pang, X., & Zhou, H.-X. (2011) · Structure · doi:10.1016/j.str.2011.10.015 · Cited by 113 · see citing works
Nielsen, J. E., Gunner, M. R., & Bertrand García‐Moreno, E. (2011) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.23194 · Cited by 112 · see citing works
Gao, M., & Skolnick, J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117768109 · Cited by 99 · see citing works
Electrostatic Properties of Protein-Protein Complexes
Kundrotas, P. J., & Alexov, E. G. (2006) · Biophysical Journal · doi:10.1529/biophysj.106.086025 · Cited by 93 · see citing works
Self-citationCalculation of Weak Protein-Protein Interactions: The pH Dependence of the Second Virial Coefficient
Elcock, A. H., & McCammon, J. A. (2001) · Biophysical Journal · doi:10.1016/s0006-3495(01)76042-0 · Cited by 92 · see citing works
Orlien, V., Boserup, L., & Olsen, K. (2010) · Journal of Dairy Science · doi:10.3168/jds.2009-2244 · Cited by 91 · see citing works
Pascalis, A. R. D., Jelesarov, I., Ackermann, F., et al. (1993) · Protein Science · doi:10.1002/pro.5560020707 · Cited by 91 · see citing works
Pan, D., & Guo, Y. (2010) · International Dairy Journal · doi:10.1016/j.idairyj.2010.01.007 · Cited by 88 · see citing works
Numerical calculations of the pH of maximal protein stability
Alexov, E. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03917.x · Cited by 84 · see citing works
Self-citationFornabaio, M., Cozzini, P., Mozzarelli, A., Abraham, D. J., & Kellogg, G. E. (2003) · Journal of Medicinal Chemistry · doi:10.1021/jm0302593 · Cited by 83 · see citing works
Davis, S. J., Davies, E., Tucknott, M. G., Jones, E. Y., & van der Merwe, P. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.10.5490 · Cited by 81 · see citing works
Deciphering the role of pH in the binding of Ciprofloxacin Hydrochloride to Bovine Serum Albumin
Anand, U., Kurup, L., & Mukherjee, S. (2012) · Physical Chemistry Chemical Physics · doi:10.1039/c2cp00001f · Cited by 79 · see citing works
Czodrowski, P., Sotriffer, C., & Klebe, G. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.01.022 · Cited by 78 · see citing works
The pH Dependency of the Binding of Drugs to Plasma Proteins in Man
Hinderling, P. H., & Hartmann, D. (2005) · Therapeutic Drug Monitoring · doi:10.1097/00007691-200502000-00014 · Cited by 77 · see citing works
Luo, S., Blom, A. M., Rupp, S., Hipler, U., Hube, B., Skerka, C., & Zipfel, P. F. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.130138 · Cited by 69 · see citing works
Mészáros, B., Simon, I., & Dosztányi, Z. (2011) · Physical Biology · doi:10.1088/1478-3975/8/3/035003 · Cited by 68 · see citing works
The effect of ligand-based tautomer and protomer prediction on structure-based virtual screening.
Kalliokoski, T., Salo, H. S., Lahtela-Kakkonen, M., & Poso, A. (2009) · Journal of Chemical Information and Modeling · doi:10.1021/ci900364w · Cited by 66 · see citing works
Residues in the H+ Translocation Site Define the pKa for Sugar Binding to LacY
Смирнова, И. Н., Kasho, V. N., Sugihara, J., Choe, J., & Kaback, H. R. (2009) · Biochemistry · doi:10.1021/bi9011918 · Cited by 62 · see citing works
Optimization of Electrostatic Interactions in Protein-Protein Complexes
Brock, K. P., Talley, K., Coley, K., Kundrotas, P. J., & Alexov, E. G. (2007) · Biophysical Journal · doi:10.1529/biophysj.107.112367 · Cited by 61 · see citing works
Self-citationJorgensen, F., Hansen, T. B., & Knøchel, S. (1999) · Food Microbiology · doi:10.1006/fmic.1998.0222 · Cited by 59 · see citing works
Prediction of Protein-Protein Association Rates from a Transition-State Theory
Alsallaq, R. A., & Zhou, H. (2007) · Structure · doi:10.1016/j.str.2007.01.005 · Cited by 59 · see citing works
Considerations in Compound Database Preparation“Hidden” Impact on Virtual Screening Results
Knox, A. J. S., Meegan, M. J., Carta, G., & Lloyd, D. G. (2005) · Journal of Chemical Information and Modeling · doi:10.1021/ci050185z · Cited by 58 · see citing works
On the electrostatic component of protein-protein binding free energy
Talley, K., Ng, C. S., Shoppell, M., Kundrotas, P. J., & Alexov, E. (2008) · PMC Biophysics · doi:10.1186/1757-5036-1-2 · Cited by 56 · see citing works
Self-citationIn silico modeling of pH‐optimum of protein–protein binding
Mitra, R. C., Zhang, Z., & Alexov, E. G. (2010) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22931 · Cited by 54 · see citing works
Self-citationElectrostatic specificity in molecular ligand design
Kangas, E., & Tidor, B. (2000) · The Journal of Chemical Physics · doi:10.1063/1.481522 · Cited by 53 · see citing works
Statistics and Physical Origins of pK and Ionization State Changes upon Protein-Ligand Binding
Aguilar, B. H., Anandakrishnan, R., Ruscio, J. Z., & Onufriev, A. V. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2009.11.016 · Cited by 52 · see citing works
Lambeir, A., Backmann, J., Ruiz‐Sanz, J., et al. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01254.x · Cited by 52 · see citing works
Alexov, E. (2004) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20107 · Cited by 51 · see citing works
Self-citationKorzhnev, D. M., Bezsonova, I., Evanics, F., et al. (2006) · Journal of the American Chemical Society · doi:10.1021/ja0601540 · Cited by 48 · see citing works
pH-dependence of the specific binding of Cu(II) and Zn(II) ions to the amyloid-β peptide
Ghalebani, L., Wahlström, A., Danielsson, J., Wärmländer, S. K. T. S., & Gräslund, A. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.04.043 · Cited by 48 · see citing works
DuBay, K. H., & Geissler, P. L. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.05.068 · Cited by 46 · see citing works
Chandran, S., Asghar, L. F. A., & Mantha, N. (2008) · Indian Journal of Pharmaceutical Sciences · doi:10.4103/0250-474x.45397 · Cited by 46 · see citing works
Sprague, E. R., Martin, W. L., & Björkman, P. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313281200 · Cited by 45 · see citing works
Estimating binding affinities by docking/scoring methods using variable protonation states
Park, M., Gao, C., & Stern, H. A. (2010) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22883 · Cited by 45 · see citing works
Maiti, A., & Drohat, A. C. (2011) · DNA repair · doi:10.1016/j.dnarep.2011.03.004 · Cited by 44 · see citing works
glmS Riboswitch Binding to the Glucosamine-6-phosphate α-Anomer Shifts the pKa toward Neutrality
Davis, J., Dunican, B. F., & Strobel, S. A. (2011) · Biochemistry · doi:10.1021/bi200471c · Cited by 41 · see citing works
Analysing the pH-dependent properties of proteins using pKa calculations
Nielsen, J. E. (2006) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2006.05.007 · Cited by 40 · see citing works
Developing hybrid approaches to predict p K a values of ionizable groups
Witham, S., Talley, K., Wang, L., Zhang, Z., Sarkar, S., Gao, D., Yang, W. Y., & Alexov, E. G. (2011) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.23097 · Cited by 37 · see citing works
Self-citationCalculating pH and Salt Dependence of Protein-Protein Binding
Jensen, J. H. (2008) · Current Pharmaceutical Biotechnology · doi:10.2174/138920108783955146 · Cited by 36 · see citing works
Bogdanović, G. A., & Novaković, S. B. (2011) · CrystEngComm · doi:10.1039/c1ce06212c · Cited by 29 · see citing works
Mitra, R. C., Shyam, R., Mitra, I., et al. (2008) · Current Computer - Aided Drug Design · doi:10.2174/157340908785747393 · Cited by 25 · see citing works
Parkes, J. H., Gibson, S. K., & Liebman, P. A. (1999) · Biochemistry · doi:10.1021/bi9827666 · Cited by 25 · see citing works
Kaushik, J. K., Iimura, S., Ogasahara, K., Yamagata, Y., Segawa, S.-I., & Yutani, K. (2006) · Biochemistry · doi:10.1021/bi052610n · Cited by 24 · see citing works
Bayden, A. S., Fornabaio, M., Scarsdale, J. N., et al. (2009) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-009-9270-7 · Cited by 24 · see citing works
Automated site preparation in physics‐based rescoring of receptor ligand complexes
Rapp, C. S., Schonbrun, C., Jacobson, M. P., Kalyanaraman, C., & Huang, N. (2009) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22415 · Cited by 22 · see citing works
Binding of the ERα Nuclear Receptor to DNA Is Coupled to Proton Uptake
Deegan, B. J., Seldeen, K. L., McDonald, C. B., Bhat, V. S., & Farooq, A. (2010) · Biochemistry · doi:10.1021/bi1004359 · Cited by 20 · see citing works
Todorov, N. P., Monthoux, P. H., & Alberts, I. L. (2006) · Journal of Chemical Information and Modeling · doi:10.1021/ci050071n · Cited by 20 · see citing works
Calculations of pH-Dependent Binding of Proteins to Biological Membranes
Mihajlovic, M., & Lazaridis, T. (2006) · The Journal of Physical Chemistry B · doi:10.1021/jp055906b · Cited by 17 · see citing works
Parkes, J. H., Gibson, S. K., & Liebman, P. A. (1999) · Biochemistry · doi:10.1021/bi995078a · Cited by 15 · see citing works
Role of Electrostatic Interactions in Binding of Thrombin to the Fibrinogen γ′ Chain
Alexander, K., Fried, M. G., & Farrell, D. H. (2012) · Biochemistry · doi:10.1021/bi2016519 · Cited by 14 · see citing works
pH Dependence of the Efficiency of Binding of Iron Cations to the Donor Side of Photosystem II
Semin, B. К., Davletshina, L. N., Aleksandrov, A. Y., et al. (2004) · Biochemistry (Moscow) · doi:10.1023/b:biry.0000022066.38297.8a · Cited by 13 · see citing works
Protonation and Anion Binding Control the Kinetics of Iron Release from Human Transferrin
Kumar, R., & Mauk, A. G. (2012) · The Journal of Physical Chemistry B · doi:10.1021/jp205879h · Cited by 12 · see citing works
Transduction mechanisms in cellular signaling
Dennis, E. A., & Bradshaw, R. A. (2011) · Academic Press eBooks · Cited by 11 · see citing works
Kearney, A., Avramovic, A., Castro, M. A. A., Carmo, A. M., Davis, S. J., & van der Merwe, P. A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700829200 · Cited by 11 · see citing works
Analysis of protein-protein interaction sites using surface patches
Jones, S., & Thornton, J. (1997) · UCL Discovery (University College London) · Cited by 10 · see citing works
Khare, P., White, A. R., & Parsons, S. M. (2009) · Biochemistry · doi:10.1021/bi900759v · Cited by 9 · see citing works
pH dependence of binding benzo[h]quinoline and humic acid and effects on fluorescence quenching
Hsieh, P.-C., Hsu, S.-H., Lee, C., et al. (2010) · Environmental Toxicology and Chemistry · doi:10.1002/etc.220 · Cited by 9 · see citing works
Kundrotas, P. J., Georgieva, P., Shosheva, A. C., et al. (2007) · Journal of Bioinformatics and Computational Biology · doi:10.1142/s0219720007002709 · Cited by 6 · see citing works
Radić, Z., Kirchhoff, P. D., Quinn, D. M., et al. (1998) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)89415-2 · Cited by 5 · see citing works
Mizutani, M., Takamatsu, Y., Ichinose, T., & Itai, A. (2012) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.60.183 · Cited by 3 · see citing works
Todorov, N. P., Monthoux, P. H., & Alberts, I. L. (2006) · ChemInform · doi:10.1002/chin.200630225 · Cited by 1 · see citing works
Statistics and Physical Origins of pK and Ionization State Changes Upon Protein-Ligand Binding
Aguilar, B. H., Anandakrishnan, R., Ruscio, J. Z., et al. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2009.12.2325 · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [87]Mizutani MY Takamatsu Y Ichinose T Itai A Prediction of ligand binding affinity using a multiple-conformations-multiple-protonation scheme: application to estrogen receptor alpha Chem Pharm Bull (Tokyo) 2012 60 183 94 22293477
Cited by
Sorted by citations
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
Drug design on quantum computers
(2024) · doi:10.1038/s41567-024-02411-5 · Cited by 132 · see citing works
- Authors
- Petukh, M., Stefl, S., & Alexov, E.
- Affiliations
- Clemson University (US)
- Corresponding author
- Alexov, Emil
- Venue
- Current Pharmaceutical Design
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2013-05-01
- Volume
- 19
- Issue
- 23
- Pages
- 4182-4190
- ISSN
- 1381-6128 (ISSN-L)
- PMC
- PMC3625499
- OpenAlex
- W2128629409
- Cited by
- 101
- References
- 124
- Citations by year
- 2026: 3 · 2025: 14 · 2024: 8 · 2023: 10 · 2022: 6 · 2021: 10 · 2020: 13 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 10 · 2014: 4 · 2013: 2
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Current Pharmaceutical Design (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- TigerPrints (Clemson University) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM093937)
- Topics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- protonation states, ligand-receptor interactions, pH-dependent binding, titratable groups, pKa prediction, ligand-receptor recognition, molecular docking, protein-ligand complex
- MeSH terms
- Ligands, Models, Molecular, Protein Binding, Protons, Receptors, Cell Surface
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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
