Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

A Computational Perspective on Molecular Recognition by Galectins

Author(s): Reyes Núñez-Franco, Francesca Peccati and Gonzalo Jiménez-Osés*

Volume 29, Issue 7, 2022

Published on: 04 August, 2021

Page: [1219 - 1231] Pages: 13

DOI: 10.2174/0929867328666210804093058

Price: $65

Abstract

This article presents an overview of recent computational studies dedicated to the analysis of binding between galectins and small-molecule ligands. We first present a summary of the most popular simulation techniques adopted for calculating binding poses and binding energies and then discuss relevant examples reported in the literature for the three main classes of galectins (dimeric, tandem, and chimera). We show that simulation of galectin-ligand interactions is a mature field that has proven invaluable for completing and unraveling experimental observations. Future perspectives to further improve the accuracy and cost-effectiveness of existing computational approaches will involve the development of new schemes to account for solvation and entropy effects, which represent the main current limitations to the accuracy of computational results.

Keywords: Galectins, molecular recognition, computational glycobiology, molecular dynamics, docking, binding energy.

« Previous Next »
[1]
Johannes, L.; Jacob, R.; Leffler, H. Galectins at a glance. J. Cell Sci., 2018, 131(9), jcs208884.
[http://dx.doi.org/10.1242/jcs.208884] [PMID: 29717004]
[2]
Modenutti, C.P.; Capurro, J.I.B.; Di Lella, S.; Martí, M.A. The structural biology of galectin-ligand recognition: current advances in modeling tools, protein engineering, and inhibitor design. Front Chem., 2019, 7, 823.
[http://dx.doi.org/10.3389/fchem.2019.00823] [PMID: 31850312]
[3]
Braun, E.; Gilmer, J.; Mayes, H. B.; Mobley, D. L.; Monroe, J. I.; Prasad, S.; Zuckerman, D. M. Best practices for foundations in molecular simulations [article v1.0]. Living J. Comput. Mol. Sci., 2019, 1(1), 5957.
[4]
Abrams, C.; Bussi, G. Enhanced sampling in molecular dynamics using metadynamics, replica-exchange, and temperature-acceleration. Entropy (Basel), 2014, 16(1), 163-199.
[http://dx.doi.org/10.3390/e16010163]
[5]
Abel, R.; Wang, L.; Harder, E.D.; Berne, B.J.; Friesner, R.A. Advancing drug discovery through enhanced free energy calculations. Acc. Chem. Res., 2017, 50(7), 1625-1632.
[http://dx.doi.org/10.1021/acs.accounts.7b00083] [PMID: 28677954]
[6]
Sulimov, V.B.; Kutov, D.C.; Sulimov, A.V. Advances in docking. Curr. Med. Chem., 2019, 26(42), 7555-7580.
[http://dx.doi.org/10.2174/0929867325666180904115000] [PMID: 30182836]
[7]
Yuriev, E.; Holien, J.; Ramsland, P.A. Improvements, trends, and new ideas in molecular docking: 2012-2013 in review. J. Mol. Recognit., 2015, 28(10), 581-604.
[http://dx.doi.org/10.1002/jmr.2471] [PMID: 25808539]
[8]
Hadden, J.A.; Tessier, M.B.; Fadda, E.; Woods, R.J. Calculating binding free energies for protein-carbohydrate complexes. Methods Mol. Biol., 2015, 1273, 431-465.
[http://dx.doi.org/10.1007/978-1-4939-2343-4_26] [PMID: 25753724]
[9]
Genheden, S.; Ryde, U. The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opin. Drug Discov., 2015, 10(5), 449-461.
[http://dx.doi.org/10.1517/17460441.2015.1032936] [PMID: 25835573]
[10]
Mondal, D.; Florian, J.; Warshel, A. Exploring the effectiveness of binding free energy calculations. J. Phys. Chem. B, 2019, 123(42), 8910-8915.
[http://dx.doi.org/10.1021/acs.jpcb.9b07593] [PMID: 31560539]
[11]
Muschik, W. Non-equilibrium thermodynamics and stochasticity: a phenomenological look on Jarzynski’s equality. Contin. Mech. Thermodyn., 2016, 28(6), 1887-1903.
[http://dx.doi.org/10.1007/s00161-016-0517-y]
[12]
Yang, Y.; Pan, L.; Lightstone, F.C.; Merz, K.M. The role of molecular dynamics potential of mean force calculations in the investigation of enzyme catalysis. Meth. Enzymol., 2016, 577, 1-29.
[http://dx.doi.org/10.1016/bs.mie.2016.05.040] [PMID: 27498632]
[13]
Jarzynski, C. Rare events and the convergence of exponentially averaged work values. Phys. Rev. E Stat. Nonlin. Soft Matter Phys., 2006, 73(4 Pt 2), 046105.
[http://dx.doi.org/10.1103/PhysRevE.73.046105] [PMID: 16711876]
[14]
Tandon, H.; Chakraborty, T.; Suhag, V. A concise review on the significance of QSAR in drug design. Chem. Biomol. Eng., 2019, 4(4), 45-51.
[15]
Majewski, M.; Ruiz-Carmona, S.; Barril, X. An investigation of structural stability in protein-ligand complexes reveals the balance between order and disorder. Commun. Chem., 2019, (2), 110.
[16]
Diehl, C.; Engström, O.; Delaine, T.; Håkansson, M.; Genheden, S.; Modig, K.; Leffler, H.; Ryde, U.; Nilsson, U.J.; Akke, M. Protein flexibility and conformational entropy in ligand design targeting the carbohydrate recognition domain of galectin-3. J. Am. Chem. Soc., 2010, 132(41), 14577-14589.
[http://dx.doi.org/10.1021/ja105852y] [PMID: 20873837]
[17]
Foley, B.L.; Tessier, M.B.; Woods, R.J. Carbohydrate force fields. Wiley Interdiscip. Rev. Comput. Mol. Sci., 2012, 2(4), 652-697.
[http://dx.doi.org/10.1002/wcms.89] [PMID: 25530813]
[18]
Woods, R.J. Predicting the structures of glycans, glycoproteins, and their complexes. Chem. Rev., 2018, 118(17), 8005-8024.
[http://dx.doi.org/10.1021/acs.chemrev.8b00032] [PMID: 30091597]
[19]
Jorgensen, W.L.; Chandrasekhar, J.; Madura, J.D.; Impey, R.W.; Klein, M.L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys., 1983, 79(2), 926-935.
[http://dx.doi.org/10.1063/1.445869]
[20]
Plazinska, A.; Plazinski, W. Comparison of carbohydrate force fields in molecular dynamics simulations of protein-carbohydrate complexes. J. Chem. Theory Comput., 2021, 17(4), 2575-2585.
[http://dx.doi.org/10.1021/acs.jctc.1c00071] [PMID: 33703894]
[21]
Hussain, M.S.; Azam, F.; Eldarrat, H.A.; Alkskas, I.; Mayoof, J.A.; Dammona, J.M.; Ismail, H.; Ali, M.; Arif, M.; Haque, A. Anti-inflammatory, analgesic and molecular docking studies of lanostanoic acid 3-O-α-D-glycopyranoside isolated from helichrysum stoechas. Arab. J. Chem., 2020, 13(12), 9196-9206.
[http://dx.doi.org/10.1016/j.arabjc.2020.11.004]
[22]
Jayakody, R.S.; Wijewardhane, P.; Herath, C.; Perera, S. Bergenin: a computationally proven promising scaffold for novel galectin-3 inhibitors. J. Mol. Model., 2018, 24(10), 302.
[http://dx.doi.org/10.1007/s00894-018-3831-4] [PMID: 30276553]
[23]
Arifuzzaman, M.; Hamza, A.; Zannat, S. S.; Fahad, R.; Rahman, A.; Hosen, S. M. Z.; Dash, R.; Hossain, M. K. Targeting galectin-3 by natural glycosides: a computational approach. Netw. Model. Anal. Heal. Informatics Bioinforma., 2020, 9, 14.
[24]
He, P.; Zhao, C.; Sun, X.; Du, Y. Design, synthesis and evaluation of lactoside-derived galectin-3 inhibitors. J. Carbohydr. Chem., 2019, 38(3), 151-166.
[http://dx.doi.org/10.1080/07328303.2019.1609022]
[25]
Bogoeva, V.; Rangelov, M.; Todorova, N.; Lambert, A.; Bridot, C.; Yordanova, A.; Roos, G.; Grandjean, C.; Bouckaert, J. Binding of gold(III) porphyrin by the pro-metastatic regulatory protein human galectin-3. Molecules, 2019, 24(24), 4561.
[http://dx.doi.org/10.3390/molecules24244561] [PMID: 31842510]
[26]
Gabr, M.; Rehman, A.U.; Chen, H.F. Quinoline-pyrazole scaffold as a novel ligand of galectin-3 and suppressor of TREM2 signaling. ACS Med. Chem. Lett., 2020, 11(9), 1759-1765.
[http://dx.doi.org/10.1021/acsmedchemlett.0c00330] [PMID: 32944144]
[27]
Sethi, A.; Sanam, S.; Alvala, M. New clues arising from hunt of saccharides binding to galectin 3 via 3D QSAR and docking studies. Informatics Med. Unlocked, 2020, 21, 100411.
[http://dx.doi.org/10.1016/j.imu.2020.100411]
[28]
Manzoni, F.; Ryde, U. Assessing the stability of free-energy perturbation calculations by performing variations in the method. J. Comput. Aided Mol. Des., 2018, 32(4), 529-536.
[http://dx.doi.org/10.1007/s10822-018-0110-5] [PMID: 29536221]
[29]
Miller, M.C.; Cai, C.; Wichapong, K.; Bhaduri, S.; Pohl, N.L.B.; Linhardt, R.J.; Gabius, H.J.; Mayo, K.H. Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides. Sci. Rep., 2020, 10(1), 15708.
[http://dx.doi.org/10.1038/s41598-020-72645-9] [PMID: 32973213]
[30]
Gimeno, A.; Delgado, S.; Valverde, P.; Bertuzzi, S.; Berbís, M.A.; Echavarren, J.; Lacetera, A.; Martín-Santamaría, S.; Surolia, A.; Cañada, F.J.; Jiménez-Barbero, J.; Ardá, A. Minimizing the entropy penalty for ligand binding: lessons from the molecular recognition of the histo blood-group antigens by human galectin-3. Angew. Chem. Int. Ed. Engl., 2019, 58(22), 7268-7272.
[http://dx.doi.org/10.1002/anie.201900723] [PMID: 30942512]
[31]
Caldararu, O.; Misini Ignjatović, M.; Oksanen, E.; Ryde, U. Water structure in solution and crystal molecular dynamics simulations compared to protein crystal structures. RSC Advances, 2020, 10(14), 8435-8443.
[http://dx.doi.org/10.1039/C9RA09601A]
[32]
Verteramo, M.L.; Stenström, O.; Ignjatović, M.M.; Caldararu, O.; Olsson, M.A.; Manzoni, F.; Leffler, H.; Oksanen, E.; Logan, D.T.; Nilsson, U.J.; Ryde, U.; Akke, M. Interplay between conformational entropy and solvation entropy in protein-ligand binding. J. Am. Chem. Soc., 2019, 141(5), 2012-2026.
[http://dx.doi.org/10.1021/jacs.8b11099] [PMID: 30618244]
[33]
Kraus, J.; Gupta, R.; Lu, M.; Gronenborn, A.M.; Akke, M.; Polenova, T. accurate backbone 13 C and 15 N chemical shift tensors in galectin-3 determined by MAS NMR and QM/MM: Details of structure and environment matter. ChemPhysChem, 2020, 21(13), 1436-1443.
[http://dx.doi.org/10.1002/cphc.202000249] [PMID: 32363727]
[34]
Kraus, J.; Gupta, R.; Yehl, J.; Lu, M.; Case, D.A.; Gronenborn, A.M.; Akke, M.; Polenova, T. Chemical shifts of the carbohydrate binding domain of galectin-3 from magic angle spinning NMR and hybrid quantum mechanics/molecular mechanics calculations. J. Phys. Chem. B, 2018, 122(11), 2931-2939.
[http://dx.doi.org/10.1021/acs.jpcb.8b00853] [PMID: 29498857]
[35]
Bertuzzi, S.; Gimeno, A.; Núñez-Franco, R.; Bernardo-Seisdedos, G.; Delgado, S.; Jiménez-Osés, G.; Millet, O.; Jiménez-Barbero, J.; Ardá, A. Unravelling the time scale of conformational plasticity and allostery in glycan recognition by human galectin-1. Chemistry, 2020, 26(67), 15643-15653.
[http://dx.doi.org/10.1002/chem.202003212] [PMID: 32780906]
[36]
Meynier, C.; Guerlesquin, F.; Roche, P. Computational studies of human galectin-1: role of conserved tryptophan residue in stacking interaction with carbohydrate ligands. J. Biomol. Struct. Dyn., 2009, 27(1), 49-58.
[http://dx.doi.org/10.1080/07391102.2009.10507295] [PMID: 19492862]
[37]
Sethi, A.; Sasikala, K.; Jakkula, P.; Gadde, D.; Sanam, S.; Qureshi, I.A.; Talla, V.; Alvala, M. Design, synthesis and computational studies involving indole-coumarin hybrids as galectin-1 inhibitors. Chem. Pap., 2021, 75, 279-285.
[http://dx.doi.org/10.1007/s11696-021-01534-w]
[38]
Sridhar Goud, N.; Pooladanda, V.; Muni Chandra, K.; Lakshmi Soukya, P.S.; Alvala, R.; Kumar, P.; Nagaraj, C.; Dawn Bharath, R.; Qureshi, I.A.; Godugu, C.; Alvala, M. Novel benzimidazole-triazole hybrids as apoptosis inducing agents in lung cancer: Design, synthesis, 18F-radiolabeling & galectin-1 inhibition studies. Bioorg. Chem., 2020, 102, 104125.
[http://dx.doi.org/10.1016/j.bioorg.2020.104125] [PMID: 32738568]
[39]
Goud, N.S.; Kanth Makani, V.K.; Pranay, J.; Alvala, R.; Qureshi, I.A.; Kumar, P.; Bharath, R.D.; Nagaraj, C.; Yerramsetty, S.; Pal-Bhadra, M.; Alvala, M. Synthesis, 18F-radiolabeling and apoptosis inducing studies of novel 4, 7-disubstituted coumarins. Bioorg. Chem., 2020, 97, 103663.
[http://dx.doi.org/10.1016/j.bioorg.2020.103663] [PMID: 32106038]
[40]
Modenutti, C.; Gauto, D.; Radusky, L.; Blanco, J.; Turjanski, A.; Hajos, S.; Marti, M. Using crystallographic water properties for the analysis and prediction of lectin-carbohydrate complex structures. Glycobiology, 2015, 25(2), 181-196.
[http://dx.doi.org/10.1093/glycob/cwu102] [PMID: 25267604]
[41]
Mahanti, M.; Pal, K.B.; Sundin, A.P.; Leffler, H.; Nilsson, U.J. Epimers Switch Galectin-9 Domain Selectivity: 3N-Aryl Galactosides Bind the C-Terminal and Gulosides Bind the N-Terminal. ACS Med. Chem. Lett., 2019, 11(1), 34-39.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00396] [PMID: 31938460]
[42]
Bohari, M.H.; Yu, X.; Kishor, C.; Patel, B.; Go, R.M.; Eslampanah Seyedi, H.A.; Vinik, Y.; Grice, I.D.; Zick, Y.; Blanchard, H. Structure-based design of a monosaccharide ligand targeting galectin-8. ChemMedChem, 2018, 13(16), 1664-1672.
[http://dx.doi.org/10.1002/cmdc.201800224] [PMID: 29926535]
[43]
Patel, B.; Kishor, C.; Houston, T.A.; Shatz-Azoulay, H.; Zick, Y.; Vinik, Y.; Blanchard, H. Rational Design and Synthesis of Methyl-β-d-galactomalonyl Phenyl Esters as Potent Galectin-8N Antagonists. J. Med. Chem., 2020, 63(20), 11573-11584.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00602] [PMID: 32809817]
[44]
Thomas, L.; Mathew, S.; Johnson, S. In-silico prediction of role of chitosan, chondroitin sulphate and agar in process of wound healing towards scaffold development. Inform. Med. Unlocked, 2020, 20, 100406.
[http://dx.doi.org/10.1016/j.imu.2020.100406]
[45]
Yukami, T.; Hasegawa, M.; Matsushita, Y.; Fujita, T.; Matsushita, T.; Horikawa, M.; Komura, K.; Yanaba, K.; Hamaguchi, Y.; Nagaoka, T.; Ogawa, F.; Fujimoto, M.; Steeber, D.A.; Tedder, T.F.; Takehara, K.; Sato, S. Endothelial selectins regulate skin wound healing in cooperation with L-selectin and ICAM-1. J. Leukoc. Biol., 2007, 82(3), 519-531.
[http://dx.doi.org/10.1189/jlb.0307152] [PMID: 17595378]
[46]
Parasuraman, P.; Murugan, V.; Selvin, J.F.A.; Gromiha, M.M.; Fukui, K.; Veluraja, K. Theoretical investigation on the glycan-binding specificity of Agrocybe cylindracea galectin using molecular modeling and molecular dynamics simulation studies. J. Mol. Recognit., 2015, 28(9), 528-538.
[http://dx.doi.org/10.1002/jmr.2468] [PMID: 25760468]
[47]
Parasuraman, P.; Selvin, J.F.A.; Gromiha, M.M.; Fukui, K.; Veluraja, K. Investigation on the binding specificity of agrocybe cylindracea galectin towards α(2,6)-linked sialyllactose by molecular modeling and molecular dynamics simulations. J. Carbohydr. Chem., 2019, 38(9), 566-585.
[http://dx.doi.org/10.1080/07328303.2019.1631323]
[48]
Yasin, N.; Laxmanappa, H.S.; Muddapur, U.M.; Cheruvathur, J.; Prakash, S.M.U.; Thulasiram, H.V. Structural, molecular, functional and immunological characterization of Wuchereria bancrofti-galectin. Int. J. Biol. Macromol., 2020, 150, 206-217.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.02.024] [PMID: 32035155]
[49]
Eckardt, V.; Miller, M.C.; Blanchet, X.; Duan, R.; Leberzammer, J.; Duchene, J.; Soehnlein, O.; Megens, R.T.; Ludwig, A.K.; Dregni, A.; Faussner, A.; Wichapong, K.; Ippel, H.; Dijkgraaf, I.; Kaltner, H.; Döring, Y.; Bidzhekov, K.; Hackeng, T.M.; Weber, C.; Gabius, H.J.; von Hundelshausen, P.; Mayo, K.H. Chemokines and galectins form heterodimers to modulate inflammation. EMBO Rep., 2020, 21(4), e47852.
[http://dx.doi.org/10.15252/embr.201947852] [PMID: 32080959]
[50]
Lenza, M.P.; Oyenarte, I.; Diercks, T.; Quintana, J.I.; Gimeno, A.; Coelho, H.; Diniz, A.; Peccati, F.; Delgado, S.; Bosch, A.; Valle, M.; Millet, O.; Abrescia, N.G.A.; Palazón, A.; Marcelo, F.; Jiménez-Osés, G.; Jiménez-Barbero, J.; Ardá, A.; Ereño-Orbea, J. Structural characterization of N-linked glycans in the receptor binding domain of the SARS-CoV-2 spike protein and their interactions with human lectins. Angew. Chem. Int. Ed. Engl., 2020, 59(52), 23763-23771.
[http://dx.doi.org/10.1002/anie.202011015] [PMID: 32915505]

Rights & Permissions Print Cite
Article Metrics
18
1
© 2024 Bentham Science Publishers | Privacy Policy