Structure-based prediction of protein allostery
Open accessAbstract
Allostery is the functional change at one site on a protein caused by a change at a distant site. In order for the benefits of allostery to be taken advantage of, both for basic understanding of proteins and to develop new classes of drugs, the structure-based prediction of allosteric binding sites, modulators and communication pathways is necessary. Here we review the recently emerging field of allosteric prediction, focusing mainly on computational methods. We also describe the search for cryptic binding pockets and attempts to design allostery into proteins. The development and adoption of such methods is essential or the long-preached potential of allostery will remain elusive.
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?
Allosteric modulators can change protein/substrate affinity in a highly predictable manner by stabilizing target proteins in inactive or active state, leading to desirable controllability.
“Allosteric modulators can change the protein/substrate affinity in a highly predictable manner by stabilizing target proteins in an inactive or active state, leading to desirable controllability.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [237]
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
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00129-0 · Cited by 18,139 · see citing works
The role of dynamic conformational ensembles in biomolecular recognition
Boehr, D. D., Nussinov, R., & Wright, P. E. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.232 · Cited by 2,008 · see citing works
Fpocket: An open source platform for ligand pocket detection
Guilloux, V. L., Schmidtke, P., & Tufféry, P. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-168 · Cited by 1,666 · see citing works
The ensemble nature of allostery
Motlagh, H. N., Wrabl, J. O., Li, J., & Hilser, V. J. (2014) · Nature · doi:10.1038/nature13001 · Cited by 1,247 · see citing works
Evolutionarily conserved networks of residues mediate allosteric communication in proteins
Süel, G. M., Lockless, S. W., Wall, M. A., & Ranganathan, R. (2002) · Nature Structural Biology · doi:10.1038/nsb881 · Cited by 816 · see citing works
Allostery in Disease and in Drug Discovery
Nussinov, R., & Tsai, C. (2013) · Cell · doi:10.1016/j.cell.2013.03.034 · Cited by 764 · see citing works
Allostery and cooperativity revisited
Cui, Q., & Karplus, M. (2008) · Protein Science · doi:10.1110/ps.03259908 · Cited by 680 · see citing works
Kozakov, D., Grove, L. E., Hall, D. R., Bohnuud, T., Mottarella, S. E., Luo, L., Xia, B., Beglov, D., & Vajda, S. (2015) · Nature Protocols · doi:10.1038/nprot.2015.043 · Cited by 643 · see citing works
Dynamically driven protein allostery
Popovych, N., Sun, S., Ebright, R. H., & Kalodimos, C. G. (2006) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1132 · Cited by 637 · see citing works
Structural Basis for Allosteric Regulation of the Monomeric Allosteric Enzyme Human Glucokinase
Kamata, K., Mitsuya, M., Nishimura, T., Eiki, J., & Nagata, Y. (2004) · Structure · doi:10.1016/j.str.2004.02.005 · Cited by 502 · see citing works
Emerging paradigms in GPCR allostery: implications for drug discovery
Wootten, D., Christopoulos, A., & Sexton, P. M. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4052 · Cited by 498 · see citing works
LIGSITEcsc: predicting ligand binding sites using the Connolly surface and degree of conservation.
Huang, B., & Schroeder, M. (2006) · BMC Structural Biology · doi:10.1186/1472-6807-6-19 · Cited by 465 · see citing works
Dobson, A. J., Chaston, J. M., Newell, P. D., Donahue, L. R., Hermann, S. L., Sannino, D. R., Westmiller, S., Wong, A. C.-N., Clark, A. G., Lazzaro, B. P., et al. (2015) · Nature Communications · doi:10.1038/ncomms8296 · Cited by 445 · see citing works
The Origin of Allosteric Functional Modulation: Multiple Pre-existing Pathways
del Sol, A., Tsai, C., Ma, B., & Nussinov, R. (2009) · Structure · doi:10.1016/j.str.2009.06.008 · Cited by 365 · see citing works
Hot Spots for Allosteric Regulation on Protein Surfaces
Reynolds, K. A., McLaughlin, R. N., & Ranganathan, R. (2011) · Cell · doi:10.1016/j.cell.2011.10.049 · Cited by 350 · see citing works
Engineering an allosteric transcription factor to respond to new ligands
Taylor, N. D., Garruss, A. S., Moretti, R., Chan, S., Arbing, M. A., Cascio, D., Rogers, J. K., Isaacs, F. J., Kosuri, S., Baker, D., et al. (2016) · Nature Methods · doi:10.1038/nmeth.3696 · Cited by 328 · see citing works
Cimermančič, P., Weinkam, P., Rettenmaier, T. J., Bichmann, L., Keedy, D. A., Woldeyes, R. A., Schneidman‐Duhovny, D., Demerdash, O., Mitchell, J. C., Wells, J. A., et al. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.01.029 · Cited by 277 · see citing works
Drugs for Allosteric Sites on Receptors
Wenthur, C. J., Gentry, P. R., Mathews, T. P., & Lindsley, C. W. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134525 · Cited by 274 · see citing works
Controlling Allosteric Networks in Proteins
Dokholyan, N. V. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00544 · Cited by 260 · see citing works
Engineering extrinsic disorder to control protein activity in living cells
Dağliyan, O., Tarnawski, M., Chu, P.-H., Shirvanyants, D. G., Schlichting, I., Dokholyan, N. V., & Hahn, K. M. (2016) · Science · doi:10.1126/science.aah3404 · Cited by 241 · see citing works
Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike
Ozorowski, G., Pallesen, J., de Val, N., Lyumkis, D., Cottrell, C. A., Torres, J. L., Copps, J., Stanfield, R. L., Cupo, A., Pugach, P., et al. (2017) · Nature · doi:10.1038/nature23010 · Cited by 238 · see citing works
Emerging Computational Methods for the Rational Discovery of Allosteric Drugs
Wagner, J., Lee, C. T., Durrant, J. D., Malmstrom, R. D., Feher, V. A., & Amaro, R. E. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00631 · Cited by 230 · see citing works
Allosite: a method for predicting allosteric sites
Huang, W., Lu, S., Huang, Z., Liu, X., Mou, L., Luo, Y., Zhao, Y., Liu, Y., Chen, Z., Hou, T., et al. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt399 · Cited by 227 · see citing works
Moult, J., Fidelis, K. A., Kryshtafovych, A., Schwede, T. F., & Tramontano, A. L. (2016) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.25064 · Cited by 226 · see citing works
Understanding Cryptic Pocket Formation in Protein Targets by Enhanced Sampling Simulations
Oleinikovas, V., Saladino, G., Cossins, B. P., & Gervasio, F. L. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b05425 · Cited by 220 · see citing works
Discovery of multiple hidden allosteric sites by combining Markov state models and experiments
Bowman, G. R., Bolin, E. R., Hart, K. M., Maguire, B. C., & Marqusee, S. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417811112 · Cited by 212 · see citing works
Allostery without a conformational change? Revisiting the paradigm
Nussinov, R., & Tsai, C.-J. (2015) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2014.11.005 · Cited by 202 · see citing works
Profiling of engineering hotspots identifies an allosteric CRISPR-Cas9 switch
Oakes, B. L., Nadler, D. C., Flamholz, A. I., Fellmann, C., Staahl, B. T., Doudna, J., & Savage, D. (2016) · Nature Biotechnology · doi:10.1038/nbt.3528 · Cited by 201 · see citing works
Origins of coevolution between residues distant in protein 3D structures
Anishchenko, I., Ovchinnikov, S., Kamisetty, H., & Baker, D. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1702664114 · Cited by 185 · see citing works
Li, S., Niu, J., Zhao, Y., So, K. P., Wang, C., Wang, C. A., & Li, J. (2017) · Nature Communications · doi:10.1038/ncomms16174 · Cited by 159 · see citing works
Brecher, M. B., Li, Z., Liu, B., Zhang, J., Koetzner, C. A., Alifarag, A. M., Jones, S. A., Lin, Q., Kramer, L. D., & Li, H. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006411 · Cited by 158 · see citing works
Structure-based model of allostery predicts coupling between distant sites
Weinkam, P., Pons, J., & Šali, A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116274109 · Cited by 157 · see citing works
Allosteric sites: remote control in regulation of protein activity
Guarnera, E., & Berezovsky, I. N. (2015) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2015.10.004 · Cited by 149 · see citing works
PARS: a web server for the prediction of Protein Allosteric and Regulatory Sites
Panjkovich, A., & Daura, X. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu002 · Cited by 139 · see citing works
AlloPred: prediction of allosteric pockets on proteins using normal mode perturbation analysis
Greener, J. G., & Sternberg, M. J. E. (2015) · BMC Bioinformatics · doi:10.1186/s12859-015-0771-1 · Cited by 134 · see citing works
Self-citationAlloSigMA: allosteric signaling and mutation analysis server
Guarnera, E., Tan, Z. W., Zheng, Z., & Berezovsky, I. N. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btx430 · Cited by 129 · see citing works
Rational design of a ligand-controlled protein conformational switch
Dağliyan, O., Shirvanyants, D. G., Karginov, A. V., Ding, F., Fee, L. R., Chandrasekaran, S. N., Freisinger, C. M., Smolen, G. A., Anna Huttenlocher, A., Hahn, K. M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218319110 · Cited by 128 · see citing works
ASD v3.0: unraveling allosteric regulation with structural mechanisms and biological networks
Shen, Q., Wang, G., Li, S., Liu, X., Lu, S., Chen, Z., Song, K., Yan, J., Geng, L., Huang, Z., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv902 · Cited by 122 · see citing works
Unraveling structural mechanisms of allosteric drug action
Nussinov, R., & Tsai, C.-J. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.03.006 · Cited by 119 · see citing works
A small-molecule allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase
Wellington, S., Nag, P. P., Michalska, K., Johnston, S. E., Jedrzejczak, R. P., Kaushik, V. K., Clatworthy, A. E., Siddiqi, N., McCarren, P. R., Bajrami, B., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2420 · Cited by 118 · see citing works
Prediction of allosteric sites and mediating interactions through bond-to-bond propensities
Amor, B., Schaub, M. T., Yaliraki, S. N., & Barahona, M. (2016) · Nature Communications · doi:10.1038/ncomms12477 · Cited by 115 · see citing works
Kinetic response of a photoperturbed allosteric protein
Stucki-Buchli, B., Waldauer, S. A., Walser, R., Donten, M. L., Pfister, R., Blöchliger, N., Steiner, S., Caflisch, A., Zerbe, O., & Hamm, P. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1306323110 · Cited by 113 · see citing works
Moving Beyond Active-Site Detection: MixMD Applied to Allosteric Systems
Ghanakota, P., & Carlson, H. A. (2016) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.6b03515 · Cited by 110 · see citing works
ASBench: benchmarking sets for allosteric discovery
Huang, W., Wang, G., Shen, Q., Liu, X., Lu, S., Geng, L., Huang, Z., & Zhang, J. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv169 · Cited by 107 · see citing works
Agonism/antagonism switching in allosteric ensembles
Motlagh, H. N., & Hilser, V. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120519109 · Cited by 102 · see citing works
Recent computational advances in the identification of allosteric sites in proteins
Lu, S., Huang, W., & Zhang, J. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.07.012 · Cited by 102 · see citing works
SPACER: server for predicting allosteric communication and effects of regulation
Goncearenco, A., Mitternacht, S., Yong, T., Eisenhaber, B., Eisenhaber, F., & Berezovsky, I. N. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt460 · Cited by 102 · see citing works
Hidden electrostatic basis of dynamic allostery in a PDZ domain
Kumawat, A., & Chakrabarty, S. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705311114 · Cited by 97 · see citing works
Entropy redistribution controls allostery in a metalloregulatory protein
Capdevila, D. A., Braymer, J. J., Edmonds, K. A., Wu, H., & Giedroc, D. P. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620665114 · Cited by 96 · see citing works
A Novel Approach to the Discovery of Small‐Molecule Ligands of CDK2
Martin, M. P., Alam, R., Betzi, S., Ingles, D. J., Zhu, J., & Schönbrunn, E. (2012) · ChemBioChem · doi:10.1002/cbic.201200316 · Cited by 91 · see citing works
Chemical, Target, and Bioactive Properties of Allosteric Modulation
van Westen, G. J. P., Gaulton, A., & Overington, J. P. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003559 · Cited by 88 · see citing works
Binding Leverage as a Molecular Basis for Allosteric Regulation
Mitternacht, S., & Berezovsky, I. N. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002148 · Cited by 85 · see citing works
Exploiting protein flexibility to predict the location of allosteric sites
Panjkovich, A., & Daura, X. (2012) · BMC Bioinformatics · doi:10.1186/1471-2105-13-273 · Cited by 83 · see citing works
Free energy landscape of activation in a signaling protein at atomic resolution
Pontiggia, F., Pachov, D. V., Clarkson, M. W., Villali, J., Hagan, M. F., Pande, V. S., & Kern, D. (2015) · Nature Communications · doi:10.1038/ncomms8284 · Cited by 82 · see citing works
Haselbach, D., Schrader, J., Lambrecht, F., Henneberg, F., Chari, A., & Stark, H. (2017) · Nature Communications · doi:10.1038/ncomms15578 · Cited by 79 · see citing works
Design of protein switches based on an ensemble model of allostery
Choi, J. H., Laurent, A. H., Hilser, V. J., & Ostermeier, M. (2015) · Nature Communications · doi:10.1038/ncomms7968 · Cited by 74 · see citing works
Kaya, C., Armutlulu, A., Ekesan, Ş., & Haliloǧlu, T. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt284 · Cited by 72 · see citing works
Computational approaches to investigating allostery
Schueler‐Furman, O., & Wodak, S. J. (2016) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2016.06.017 · Cited by 72 · see citing works
Hart, K. M., Moeder, K. E., Ho, C. M. W., Zimmerman, M. I., Frederick, T. E., & Bowman, G. R. (2017) · PLoS ONE · doi:10.1371/journal.pone.0178678 · Cited by 71 · see citing works
Time-resolved observation of protein allosteric communication
Buchenberg, S., Sittel, F., & Stock, G. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1707694114 · Cited by 69 · see citing works
Singh, S., & Bowman, G. R. (2017) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.6b01181 · Cited by 65 · see citing works
Perturbation–Response Scanning Reveals Key Residues for Allosteric Control in Hsp70
Penkler, D. L., Şensoy, Ö., Atılgan, C., & Bishop, Ö. T. (2017) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.6b00775 · Cited by 65 · see citing works
Structure-Based Predictive Models for Allosteric Hot Spots
Demerdash, O., Daily, M. D., & Mitchell, J. C. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000531 · Cited by 64 · see citing works
Drug design from the cryptic inhibitor envelope
Lee, C.-J., Liang, X., Wu, Q., Najeeb, J., Zhao, J., Gopalaswamy, R., Titécat, M., Sebbane, F., Lemaître, N., Toone, E. J., et al. (2016) · Nature Communications · doi:10.1038/ncomms10638 · Cited by 64 · see citing works
Raman, S., Taylor, N. D., Genuth, N. R., Fields, S., & Church, G. M. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.09.004 · Cited by 64 · see citing works
Identifying Allosteric Hotspots with Dynamics: Application to Inter- and Intra-species Conservation
Clarke, D., Sethi, A., Li, S., Kumar, S., Chang, R. W. F., Chen, J., & Gerstein, M. (2016) · Structure · doi:10.1016/j.str.2016.03.008 · Cited by 56 · see citing works
Detrimental effects of duplicate reads and low complexity regions on RNA- and ChIP-seq data
Dozmorov, M. G., Adrianto, I., Giles, C. B., Glass, E., Glenn, S. B., Montgomery, C. G., Sivils, K. L. M., Olson, L. E., Iwayama, T., Freeman, W. M., et al. (2015) · BMC Bioinformatics · doi:10.1186/1471-2105-16-s13-s10 · Cited by 55 · see citing works
The Rrp6 C-terminal domain binds RNA and activates the nuclear RNA exosome
Wasmuth, E. V., & Lima, C. D. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1152 · Cited by 55 · see citing works
Design of Allosterically Regulated Protein Catalysts
Makhlynets, O. V., Raymond, E. A., & Korendovych, I. V. (2015) · Biochemistry · doi:10.1021/bi5015248 · Cited by 54 · see citing works
Predicting Protein Dynamics and Allostery Using Multi-Protein Atomic Distance Constraints
Greener, J. G., Filippis, I., & Sternberg, M. J. E. (2017) · Structure · doi:10.1016/j.str.2017.01.008 · Cited by 44 · see citing works
Self-citationToward understanding the molecular basis for chemical allosteric modulator design
Wang, Q., Zheng, M., Huang, Z., Liu, X., Zhou, H., Chen, Y., Shi, T., & Zhang, J. (2012) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2012.07.006 · Cited by 40 · see citing works
Energetic redistribution in allostery to execute protein function
Liu, J., & Nussinov, R. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1709071114 · Cited by 40 · see citing works
A Random Forest Model for Predicting Allosteric and Functional Sites on Proteins
Chen, A. S. ‐., Westwood, N. J., Brear, P., Rogers, G. W., Mavridis, L., & Mitchell, J. B. O. (2016) · Molecular Informatics · doi:10.1002/minf.201500108 · Cited by 35 · see citing works
Uncoupling conformational states from activity in an allosteric enzyme
Pisco, J. P., de Chiara, C., Pacholarz, K. J., Garza-Garcı́a, A., Ogrodowicz, R. W., Walker, P. A., Barran, P. E., Smerdon, S. J., & de Carvalho, L. P. S. (2017) · Nature Communications · doi:10.1038/s41467-017-00224-0 · Cited by 27 · see citing works
Event extraction of bacteria biotopes: a knowledge-intensive NLP-based approach
Ratkovic, Z., Golik, W., & Warnier, P. (2012) · BMC Bioinformatics · doi:10.1186/1471-2105-13-s11-s8 · Cited by 22 · see citing works
Exploring the limits of the usefulness of mutagenesis in studies of allosteric mechanisms
Tang, Q., Alontaga, A. Y., Holyoak, T., & Fenton, A. W. (2017) · Human Mutation · doi:10.1002/humu.23239 · Cited by 22 · see citing works
Targeting Conformational Activation of CDK2 Kinase
Pellerano, M., Tcherniuk, S. O., Pérals, C., Van, T. N. N., Garcin, E. D., Mahuteau‐Betzer, F., Teulade‐Fichou, M., & Morris, M. C. (2017) · Biotechnology Journal · doi:10.1002/biot.201600531 · Cited by 19 · see citing works
Benchmarking predictions of allostery in liver pyruvate kinase in CAGI4
Xu, Q., Tang, Q., Katsonis, P., Lichtarge, O., Jones, D. T., Bovo, S., Babbi, G., Martelli, P. L., Casadio, R., Lee, G. R., et al. (2017) · Human Mutation · doi:10.1002/humu.23222 · Cited by 17 · see citing works
Long Distance Modulation of Disorder-to-Order Transitions in Protein Allostery
Wang, J., Custer, G., Beckett, D., & Matysiak, S. (2017) · Biochemistry · doi:10.1021/acs.biochem.7b00496 · Cited by 13 · see citing works
Ye, W., Qian, T., Liu, H., Luo, R., & Chen, H. (2017) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.7b00073 · Cited by 12 · see citing works
Jayakar, S. S., Ang, G., Chiara, D. C., & Hamouda, A. K. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-6952-4_7 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Lipinski CA, Lombardo F, Dominy BW, Feeney PJ: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001, 46:3-26.
Cited by
Sorted by citations
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
AlphaFold, Artificial Intelligence (AI), and Allostery
Nussinov, R., Zhang, M., Liu, Y., & Jang, H. (2022) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.2c04346 · Cited by 190 · see citing works
Allosteric Modulator Discovery: From Serendipity to Structure-Based Design
Lu, S., He, X., Ni, D., & Zhang, J. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01749 · Cited by 176 · see citing works
Lu, S., Shen, Q., & Zhang, J. (2019) · Accounts of Chemical Research · doi:10.1021/acs.accounts.8b00570 · Cited by 166 · see citing works
In silico Methods for Design of Kinase Inhibitors as Anticancer Drugs
Gagić, Ž., Ružić, D., Djoković, N., Djikić, T., & Nikolic, K. M. (2020) · Frontiers in Chemistry · doi:10.3389/fchem.2019.00873 · Cited by 144 · see citing works
Nussinov, R., Jang, H., Tsai, C., & Cheng, F. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006658 · Cited by 129 · see citing works
Sequence-based drug design as a concept in computational drug design
Chen, L., Fan, Z., Chang, J., Yang, R., Hou, H., Guo, H., Zhang, Y., Yang, T., Zhou, C., Sui, Q., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39856-w · Cited by 129 · see citing works
Intrinsic dynamics is evolutionarily optimized to enable allosteric behavior
Zhang, Y., Doruker, P., Kaynak, B., Zhang, S., Krieger, J., Li, H., & Bahar, İ. (2019) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2019.11.002 · Cited by 113 · see citing works
Hot spots-making directed evolution easier
Yu, H., Ma, S., Li, Y., & Dalby, P. A. (2022) · Biotechnology Advances · doi:10.1016/j.biotechadv.2022.107926 · Cited by 112 · see citing works
Integrated Computational Approaches and Tools for Allosteric Drug Discovery
Amamuddy, O. S., Veldman, W., Manyumwa, C. V., Khairallah, A., Agajanian, S., Odeyemi, O., Verkhivker, G. M., & Bishop, Ö. T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21030847 · Cited by 105 · see citing works
On the perturbation nature of allostery: sites, mutations, and signal modulation
Guarnera, E., & Berezovsky, I. N. (2018) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2018.10.008 · Cited by 105 · see citing works
AlloFinder: a strategy for allosteric modulator discovery and allosterome analyses
Huang, M., Song, K., Liu, X., Lu, S., Shen, Q., Wang, R., Gao, J., Hong, Y., Li, Q., Ni, D., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky374 · Cited by 92 · see citing works
Rational design of allosteric modulators: Challenges and successes
Chatzigoulas, A., & Cournia, Z. (2021) · Wiley Interdisciplinary Reviews Computational Molecular Science · doi:10.1002/wcms.1529 · Cited by 87 · see citing works
Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs
Nussinov, R., Zhang, M., Maloney, R., Liu, Y., Tsai, C.-J., & Jang, H. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167569 · Cited by 66 · see citing works
AlloMAPS: allosteric mutation analysis and polymorphism of signaling database
Tan, Z. W., Tee, W.-V., Guarnera, E., Booth, L., & Berezovsky, I. N. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1028 · Cited by 66 · see citing works
Kaynak, B., Bahar, İ., & Doruker, P. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.06.020 · Cited by 65 · see citing works
Kjer-Hansen, P., & Weatheritt, R. J. (2023) · Nature Structural & Molecular Biology · doi:10.1038/s41594-023-01155-9 · Cited by 66 · see citing works
Generalizable Protein Biosensors Based on Synthetic Switch Modules
Guo, Z., Johnston, W. A., Whitfield, J. H., Walden, P. M., Cui, Z., Wijker, E., Edwardraja, S., Lantadilla, I. R., Ely, F., Vickers, C. E., et al. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.8b12298 · Cited by 61 · see citing works
Machine learning approaches in predicting allosteric sites
Nerín-Fonz, F., & Cournia, Z. (2024) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2024.102774 · Cited by 61 · see citing works
Advanced Methods for Accessing Protein Shape-Shifting Present New Therapeutic Opportunities
Knoverek, C. R., Amarasinghe, G. K., & Bowman, G. R. (2018) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2018.11.007 · Cited by 55 · see citing works
Allosteric small molecule modulators of nuclear receptors
Meijer, F. A., de Gevel, I. A. L.-V., de Vries, R. M. J. M., & Brunsveld, L. (2019) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2019.01.022 · Cited by 50 · see citing works
Why Are Some Driver Mutations Rare?
Nussinov, R., Tsai, C., & Jang, H. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.10.003 · Cited by 47 · see citing works
Allosteric regulation of CRISPR-Cas9 for DNA-targeting and cleavage
Zuo, Z., & Liu, J. (2020) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2020.01.013 · Cited by 48 · see citing works
Tsuchiya, Y., Taneishi, K., & Yonezawa, Y. (2019) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.9b00426 · Cited by 45 · see citing works
Water-mediated biomolecular dynamics and allostery
Leitner, D. M., Hyeon, C., & Reid, K. M. (2020) · The Journal of Chemical Physics · doi:10.1063/5.0011392 · Cited by 44 · see citing works
Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A
Friberg, A., Rehwinkel, H., Nguyen, D., Pütter, V., Quanz, M., Weiske, J., Eberspächer, U., Heisler, I., & Langer, G. (2020) · ACS Omega · doi:10.1021/acsomega.0c00715 · Cited by 43 · see citing works
AlloDriver: a method for the identification and analysis of cancer driver targets
Song, K., Li, Q., Gao, W., Lu, S., Shen, Q., Liu, X., Wu, Y., Wang, B., Lin, H., Chen, G., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz350 · Cited by 40 · see citing works
Selective Modulation of Dynamic Protein Complexes
Garlick, J. M., & Mapp, A. K. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.07.019 · Cited by 34 · see citing works
Ahdab, D. E., Lagardère, L., Inizan, T. J., Célerse, F., Liu, C., Adjoua, O., Jolly, L.-H., Gresh, N., Hobaika, Z., Ren, P. Y., et al. (2021) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.1c01460 · Cited by 28 · see citing works
Designing Molecular Spanners to Throw in the Protein Networks
Serapian, S. A., & Colombo, G. (2019) · Chemistry - A European Journal · doi:10.1002/chem.201904523 · Cited by 27 · see citing works
Sen, N., Anishchenko, I., Bordin, N., Sillitoe, I., Velankar, S., Baker, D., & Orengo, C. (2022) · Briefings in Bioinformatics · doi:10.1093/bib/bbac187 · Cited by 25 · see citing works
Evolutionary-Conserved Allosteric Properties of Three Neuronal Calcium Sensor Proteins
Marino, V., & Dell’Orco, D. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00050 · Cited by 24 · see citing works
Allosteric Hotspots in the Main Protease of SARS-CoV-2
Strömich, L., Wu, N., Barahona, M., & Yaliraki, S. N. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167748 · Cited by 23 · see citing works
LOV Domains in the Design of Photoresponsive Enzymes
Seifert, S., & Brakmann, S. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.8b00159 · Cited by 23 · see citing works
Dissecting a novel allosteric mechanism of cruzain: A computer-aided approach
Alvarez, L. H., Gomes, D. E. B., González, J. E. H., & Pascutti, P. G. (2019) · PLoS ONE · doi:10.1371/journal.pone.0211227 · Cited by 23 · see citing works
Characteristics of Allosteric Proteins, Sites, and Modulators
He, X., Ni, D., Lu, S., & Zhang, J. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-8719-7_6 · Cited by 22 · see citing works
Halder, A., Anto, A., Subramanyan, V., Bhattacharyya, M., Vishveshwara, S., & Vishveshwara, S. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.596945 · Cited by 20 · see citing works
Advances in the Computational Identification of Allosteric Sites and Pathways in Proteins
Daura, X. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-8719-7_7 · Cited by 19 · see citing works
DeepMolecules: a web server for predicting enzyme and transporter–small molecule interactions
Kroll, A., Rousset, Y., Spitzlei, T., & Lercher, M. J. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf343 · Cited by 18 · see citing works
Emerging maps of allosteric regulation in cellular networks
Mathy, C. J. P., & Kortemme, T. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102602 · Cited by 17 · see citing works
Montserrat‐Canals, M., Cordara, G., & Krengel, U. (2025) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583524000209 · Cited by 18 · see citing works
Wu, N., Yaliraki, S. N., & Barahona, M. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167749 · Cited by 16 · see citing works
Recent advances suggest increased influence of selective pressure in allostery
Bhat, A., Schaeffer, R. D., Kinch, L. N., Medvedev, K. E., & Grishin, N. V. (2020) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2020.02.004 · Cited by 16 · see citing works
Study on immunogenicity and antigenicity of a novel brucella multiepitope recombined protein
Yin, D., Bai, Q., Li, L., Xu, K., & Zhang, J. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.12.098 · Cited by 14 · see citing works
Distinct allosteric pathways in imidazole glycerol phosphate synthase from yeast and bacteria
Maschietto, F., Gheeraert, A., Piazzi, A., Batista, V. S., & Rivalta, I. (2021) · Biophysical Journal · doi:10.1016/j.bpj.2021.11.2888 · Cited by 14 · see citing works
Decrypting a cryptic allosteric pocket in H. pylori glutamate racemase
Chheda, P. R., Cooling, G. T., Dean, S. F., Propp, J., Hobbs, K. F., & Spies, M. A. (2021) · Communications Chemistry · doi:10.1038/s42004-021-00605-z · Cited by 13 · see citing works
Schneider, M., & Antes, I. (2022) · PLoS ONE · doi:10.1371/journal.pone.0265194 · Cited by 13 · see citing works
Kaczor, A. A., Wróbel, T. M., & Bartuzi, D. (2022) · Molecules · doi:10.3390/molecules28010178 · Cited by 13 · see citing works
An allosteric mechanism for potent inhibition of SARS-CoV-2 main proteinase
Zhang, Y., Guo, J., Liu, Y., Qu, Y., Li, Y., Mu, Y., & Li, W. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.130644 · Cited by 13 · see citing works
Hu, F., Chang, F., Tao, L., Sun, X., Liu, L., Zhao, Y., Han, Z., & Li, C. (2024) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.4c00544 · Cited by 13 · see citing works
D’Amico, R. N., Bosken, Y. K., O’Rourke, K. F., Murray, A. M., Admasu, W., Chang, C. A., & Boehr, D. D. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.679915 · Cited by 13 · see citing works
Kakarala, K. K., & Jamil, K. (2021) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2021.1891140 · Cited by 13 · see citing works
Das, S., Roy, S., Rahaman, S. B., Akbar, S., Ahmed, B., Halder, D., Ramachandran, A. K., & Joseph, A. (2022) · Current Medicinal Chemistry · doi:10.2174/0929867329666220509112423 · Cited by 12 · see citing works
Sharapova, Y., Švedas, V. K., & Suplatov, D. A. (2020) · FEBS Journal · doi:10.1111/febs.15610 · Cited by 12 · see citing works
Identification of Allosteric Effects in Proteins by Elastic Network Models
Hu, G. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-1154-8_3 · Cited by 11 · see citing works
Structural insights into the mechanism of human methyltransferase hPRMT4
Singh, A. P., Kumar, R., & Gupta, D. K. (2021) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2021.1950567 · Cited by 10 · see citing works
Yuce, M., Sarıca, Z., Ates, B., & Kürkçüoğlu, Ö. (2022) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2022.2051743 · Cited by 9 · see citing works
Raza, S. H. A., Zhong, R., Yu, X., Zhao, G., Wei, X., & Lei, H. (2023) · Molecular Biotechnology · doi:10.1007/s12033-023-00951-4 · Cited by 9 · see citing works
RetractedNordquist, E. B., Zhang, G., Barethiya, S., Ji, N., White, K. M., Han, L., Jia, Z., Shi, J., Cui, J., & Chen, J. (2023) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1011460 · Cited by 8 · see citing works
Toussi, C. A., Haddadnia, J., & Matta, C. F. (2020) · Molecular Diversity · doi:10.1007/s11030-020-10074-6 · Cited by 8 · see citing works
Zeng, Q. H., Li, Q., Sun, D., & Zheng, M. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00565 · Cited by 8 · see citing works
Omage, F. B., Salim, J. A., Mazoni, I., Yano, I. H., González, J. E. H., Giachetto, P. F., Tasić, L., Arni, R. K., & Neshich, G. (2025) · Briefings in Bioinformatics · doi:10.1093/bib/bbaf424 · Cited by 7 · see citing works
Engineering and application of LacI mutants with stringent expressions
Wu, J., Liang, C., Li, Y., Zeng, Y., Sun, X., Jiang, P., Chen, W., Xiong, D., Jin, J., & Tang, S. (2024) · Microbial Biotechnology · doi:10.1111/1751-7915.14427 · Cited by 6 · see citing works
Payghan, P. V., Bera, I., Bhattacharyya, D., & Ghoshal, N. (2018) · Frontiers in Physics · doi:10.3389/fphy.2018.00052 · Cited by 6 · see citing works
Maity, D., & Qiao, B. (2025) · ACS Omega · doi:10.1021/acsomega.5c01263 · Cited by 5 · see citing works
Chemical and Biophysical Approaches to Allosteric Modulation
Civera, M., Moroni, E., Sorrentino, L., Vasile, F., & Sattin, S. (2021) · European Journal of Organic Chemistry · doi:10.1002/ejoc.202100506 · Cited by 6 · see citing works
Analysis of Protein Structures Using Residue Interaction Networks
Shcherbinin, D., & Veselovsky, A. V. (2019) · Challenges and advances in computational chemistry and physics · doi:10.1007/978-3-030-05282-9_3 · Cited by 5 · see citing works
Global Geometrical Constraints on the Shape of Proteins and Their Influence on Allosteric Regulation
Morikawa, N. (2018) · Applied Mathematics · doi:10.4236/am.2018.910076 · Cited by 5 · see citing works
How do mutations and allosteric inhibitors modulate caspase-7 activity? A molecular dynamics study
Bingöl, E. N., Serçinoğlu, O., & Özbek, P. (2018) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2018.1517611 · Cited by 4 · see citing works
Rocha, G. V., Bastos, L. S., & Costa, M. G. S. (2020) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.25985 · Cited by 4 · see citing works
Pore formation by pore forming membrane proteins towards infections
Sannigrahi, A., & Chattopadhyay, K. (2022) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2021.09.001 · Cited by 4 · see citing works
In silico studies of the inhibition mechanism of dengue with papain
Vasudevan, S., Ramachandran, R., Shankar, R., & Vijayakumar, S. (2020) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2020.1742205 · Cited by 4 · see citing works
Lawson, A. D. G., MacCoss, M., Baeten, D., Macpherson, A., Shi, J., & Henry, A. J. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.668186 · Cited by 4 · see citing works
Chandra, A., Goyal, N., Behera, A., Samanta, J., & Sharma, T. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-16013-4.00016-6 · Cited by 3 · see citing works
Autoencoder-based detection of the residues involved in G protein-coupled receptor signaling
Tsuchiya, Y., Taneishi, K., & Yonezawa, Y. (2021) · Scientific Reports · doi:10.1038/s41598-021-99019-z · Cited by 3 · see citing works
The role of cooperativity in a p53-miR34 dynamical mathematical model
Nikolov, S. G., Olaf Wolkenhauer, A., Vera, J., & Nenov, M. (2020) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2020.110252 · Cited by 3 · see citing works
Protein exosites as drug targets: from structural topology to therapeutic modality
Omage, F. B., Mazoni, I., Yano, I. H., & Neshich, G. (2026) · Drug Discovery Today · doi:10.1016/j.drudis.2026.104662 · Cited by 2 · see citing works
Yin, D., Bai, Q., Li, L., Xu, L., Xu, K., & Li, J. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/786343 · Cited by 2 · see citing works
Sparse group selection and analysis of function‐related residue for protein‐state recognition
Bai, F., Puk, K. M., Liu, J., Zhou, H.-Y., Tao, P., Zhou, W., & Wang, S. (2022) · Journal of Computational Chemistry · doi:10.1002/jcc.26937 · Cited by 1 · see citing works
Drug design and repurposing with a sequence-to-drug paradigmPreprint
Chen, L., Fan, Z., Chang, J., Yang, R., Guo, H., Zhang, Y., Yang, T., Zhou, C., Chen, Z., Zheng, C., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.03.26.485909 · Cited by 1 · see citing works
Dynamic Order in Allosteric InteractionsPreprint
Türeli, S., & Haliloǧlu, T. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.01.27.920850
An Ensemble Model for Protein Allosteric Site Prediction
乔, 仕. (2024) · Biophysics · doi:10.12677/biphy.2024.122004
Steric confinement-induced emission probe for monitoring protein conformations in live cells
Jia, H., Yang, L., Yang, Y., Liu, H., Liu, J., Shang, C., Di, Z., He, B., & Zhang, K. (2026) · Communications Chemistry · doi:10.1038/s42004-026-01914-x
Protein arginine methyltransferase 3: Mechanism of action in diseases and modulator discovery.
Yu, D.-M., He, K., Mai, C., & Li, M.-F. (2026) · Bioorganic chemistry (Print) · doi:10.1016/j.bioorg.2026.109589
Lu, Y., Ohara, Y., Kunugi, H., & Tateno, M. (2026) · ACS Omega · doi:10.1021/acsomega.6c04325
A systematic evaluation of protein allosteric site prediction tools with independent datasets
Ai, Y., Li, H., Huang, X., & Liu, S. (2026) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-026-00831-4
STING-ExositeDB: An AI-assisted curated database of protein exosites for drug discovery
Omage, F. B., Mazoni, I., Yano, I. H., & Neshich, G. (2026) · Database · doi:10.1093/database/baag031
Hacisuleyman, A. (2026) · SSRN Electronic Journal · doi:10.2139/ssrn.7203451
FAIRsharing record for: Allosteric Mutation Analysis and Polymorphism of Signaling database
FAIRsharing Team, & Lister, A. (2018) · FAIRsharing.org · doi:10.25504/fairsharing.aie9sa
BindingDB (2021) · UC San Diego · doi:10.7270/q2c53q9m
- Authors
- Greener, J. G., & Sternberg, M. J.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Greener, Joe G
- Venue
- Current Opinion in Structural Biology
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 50
- Pages
- 1-8
- ISSN
- 0959-440X (ISSN-L)
- OpenAlex
- W2766298563
- Cited by
- 91
- References
- 81
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 13 · 2021: 12 · 2020: 17 · 2019: 16 · 2018: 9
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Opinion in Structural Biology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/J014575/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- 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
- Keywords
- protein allostery, allosteric modulators, cryptic binding pockets, structure-based drug design, computational methods
- MeSH terms
- Allosteric Regulation, Allosteric Site, Models, Molecular, Protein Binding, Proteins, Software, Computational Biology, Quantitative Structure-Activity Relationship
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
