HSV-1 Glycoprotein D and Its Surface Receptors: Evaluation of Protein–Protein Interaction and Targeting by Triazole-Based Compounds through In Silico Approaches
Abstract
:1. Introduction
- Herpesvirus entry mediator (HVEM), a member of the tumor necrosis factor receptor superfamily (TNFR) expressed on activate lymphocytes and in other human tissues including kidney, lung, and liver;
- Nectin-1 and 2, immunoglobulin (Ig)-like cell adhesion molecules (CAMs) expressed on the surface of neuronal and epithelial cells [12];
- 3-O-sulfated heparan sulfate (3-OS HS), whose biological role has not yet been well clarified [13].
2. Results and Discussion
3. Materials and Methods
3.1. Computational Methods
3.1.1. Protein–protein Preparation of gD-HVEM and gD-Nectin-1 and Docking Simulations
3.1.2. MDs, GBPM, and MM/GBSA Calculations of gD-HVEM and gD-Nectin-1 Complexes
3.2. Structure-Based Virtual Screening of [1,2,3]triazolo[4,5-h][1,6]naphthyridines, and [1,2,3]triazolo[4,5-b]Pyridines on gD-Pocket 1 and gD-Pocket 2
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Gilbert, C.; Bestman-Smith, J.; Boivin, G. Resistance of herpesviruses to antiviral drugs: Clinical impacts and molecular mechanisms. Drug Resist. Updat. 2002, 5, 88–114. [Google Scholar] [CrossRef] [PubMed]
- De Mello, C.P.P.; Bloom, D.C.; Paixao, I.C. Herpes simplex virus type-1: Replication, latency, reactivation and its antiviral targets. Antivir. Ther. 2016, 21, 277–286. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gupta, R.; Warren, T.; Wald, A. Genital herpes. Lancet 2007, 370, 2127–2137. [Google Scholar] [CrossRef]
- Wu, J.; Power, H.; Miranda-Saksena, M.; Valtchev, P.; Schindeler, A.; Cunningham, A.L.; Dehghani, F. Identifying HSV-1 Inhibitors from Natural Compounds via Virtual Screening Targeting Surface Glycoprotein D. Pharmaceuticals 2022, 15, 361. [Google Scholar] [CrossRef] [PubMed]
- Whitley, R.; Baines, J. Clinical management of herpes simplex virus infections: Past, present, and future. F1000Research 2018, 7, F1000 Faculty Rev-1726. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sadowski, L.A.; Upadhyay, R.; Greeley, Z.W.; Margulies, B.J. Current drugs to treat infections with herpes simplex viruses-1 and-2. Viruses 2021, 13, 1228. [Google Scholar] [CrossRef] [PubMed]
- Jiang, Y.-C.; Feng, H.; Lin, Y.-C.; Guo, X.-R. New strategies against drug resistance to herpes simplex virus. Int. J. Oral Sci. 2016, 8, 1–6. [Google Scholar] [CrossRef]
- Connolly, S.A.; Jackson, J.O.; Jardetzky, T.S.; Longnecker, R. Fusing structure and function: A structural view of the herpesvirus entry machinery. Nat. Rev. Microbiol. 2011, 9, 369–381. [Google Scholar] [CrossRef]
- Spear, P.G. Herpes simplex virus: Receptors and ligands for cell entry. Cell. Microbiol. 2004, 6, 401–410. [Google Scholar] [CrossRef]
- Heldwein, E.; Krummenacher, C. Entry of herpesviruses into mammalian cells. Cell. Mol. Life Sci. 2008, 65, 1653–1668. [Google Scholar] [CrossRef]
- Connolly, S.A.; Jardetzky, T.S.; Longnecker, R. The structural basis of herpesvirus entry. Nat. Rev. Microbiol. 2021, 19, 110–121. [Google Scholar] [CrossRef] [PubMed]
- Petermann, P.; Thier, K.; Rahn, E.; Rixon, F.J.; Bloch, W.; Özcelik, S.; Krummenacher, C.; Barron, M.J.; Dixon, M.J.; Scheu, S. Entry mechanisms of herpes simplex virus 1 into murine epidermis: Involvement of nectin-1 and herpesvirus entry mediator as cellular receptors. J. Virol. 2015, 89, 262–274. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tiwari, V.; O’Donnell, C.D.; Oh, M.-J.; Valyi-Nagy, T.; Shukla, D. A role for 3-O-sulfotransferase isoform-4 in assisting HSV-1 entry and spread. Biochem. Biophys. Res. Commun. 2005, 338, 930–937. [Google Scholar] [CrossRef] [PubMed]
- Labbozzetta, M.; Barreca, M.; Spanò, V.; Raimondi, M.V.; Poma, P.; Notarbartolo, M.; Barraja, P.; Montalbano, A. Novel insights on [1, 2] oxazolo [5, 4-e] isoindoles on multidrug resistant acute myeloid leukemia cell line. Drug Dev. Res. 2022, 83, 1331–1341. [Google Scholar] [CrossRef] [PubMed]
- Barreca, M.; Spanò, V.; Rocca, R.; Bivacqua, R.; Abel, A.-C.; Maruca, A.; Montalbano, A.; Raimondi, M.V.; Tarantelli, C.; Gaudio, E. Development of [1, 2] oxazoloisoindoles tubulin polymerization inhibitors: Further chemical modifications and potential therapeutic effects against lymphomas. Eur. J. Med. Chem. 2022, 243, 114744. [Google Scholar] [CrossRef]
- Barreca, M.; Spanò, V.; Raimondi, M.V.; Tarantelli, C.; Spriano, F.; Bertoni, F.; Barraja, P.; Montalbano, A. Recurrence of the oxazole motif in tubulin colchicine site inhibitors with anti-tumor activity. Eur. J. Med. Chem. Rep. 2021, 1, 100004. [Google Scholar] [CrossRef]
- Barreca, M.; Ingarra, A.M.; Raimondi, M.V.; Spanò, V.; De Franco, M.; Menilli, L.; Gandin, V.; Miolo, G.; Barraja, P.; Montalbano, A. Insight on pyrimido [5, 4-g] indolizine and pyrimido [4, 5-c] pyrrolo [1, 2-a] azepine systems as promising photosensitizers on malignant cells. Eur. J. Med. Chem. 2022, 237, 114399. [Google Scholar] [CrossRef]
- Frasson, I.; Spano, V.; Di Martino, S.; Nadai, M.; Doria, F.; Parrino, B.; Carbone, A.; Cascioferro, S.M.; Diana, P.; Cirrincione, G. Synthesis and photocytotoxic activity of [1, 2, 3] triazolo [4, 5-h][1, 6] naphthyridines and [1, 3] oxazolo [5, 4-h][1, 6] naphthyridines. Eur. J. Med. Chem. 2019, 162, 176–193. [Google Scholar] [CrossRef]
- Seck, I.; Nguemo, F. Triazole, imidazole, and thiazole-based compounds as potential agents against coronavirus. Results Chem. 2021, 3, 100132. [Google Scholar] [CrossRef]
- Dheer, D.; Singh, V.; Shankar, R. Medicinal attributes of 1, 2, 3-triazoles: Current developments. Bioorganic Chem. 2017, 71, 30–54. [Google Scholar] [CrossRef]
- Bozorov, K.; Zhao, J.; Aisa, H.A. 1, 2, 3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview. Bioorganic Med. Chem. 2019, 27, 3511–3531. [Google Scholar] [CrossRef] [PubMed]
- Bivacqua, R.; Barreca, M.; Spanò, V.; Raimondi, M.V.; Romeo, I.; Alcaro, S.; Andrei, G.; Barraja, P.; Montalbano, A. Insight into non-nucleoside triazole-based systems as viral polymerases inhibitors. Eur. J. Med. Chem. 2023, 115136. [Google Scholar] [CrossRef] [PubMed]
- Zhuang, L.; Wai, J.S.; Embrey, M.W.; Fisher, T.E.; Egbertson, M.S.; Payne, L.S.; Guare, J.P.; Vacca, J.P.; Hazuda, D.J.; Felock, P.J. Design and synthesis of 8-hydroxy-[1, 6] naphthyridines as novel inhibitors of HIV-1 integrase in vitro and in infected cells. J. Med. Chem. 2003, 46, 453–456. [Google Scholar] [CrossRef] [PubMed]
- Falardeau, G.; Lachance, H.; St-Pierre, A.; Yannopoulos, C.G.; Drouin, M.; Bédard, J.; Chan, L. Design and synthesis of a potent macrocyclic 1, 6-napthyridine anti-human cytomegalovirus (HCMV) inhibitors. Bioorganic Med. Chem. Lett. 2005, 15, 1693–1695. [Google Scholar] [CrossRef] [PubMed]
- Embrey, M.W.; Wai, J.S.; Funk, T.W.; Homnick, C.F.; Perlow, D.S.; Young, S.D.; Vacca, J.P.; Hazuda, D.J.; Felock, P.J.; Stillmock, K.A. A series of 5-(5, 6)-dihydrouracil substituted 8-hydroxy-[1, 6] naphthyridine-7-carboxylic acid 4-fluorobenzylamide inhibitors of HIV-1 integrase and viral replication in cells. Bioorganic Med. Chem. Lett. 2005, 15, 4550–4554. [Google Scholar] [CrossRef]
- Chan, L.; Stefanac, T.; Lavallée, J.-F.; Jin, H.; Bédard, J.; May, S.; Falardeau, G. Design and synthesis of new potent human cytomegalovirus (HCMV) inhibitors based on internally hydrogen-bonded 1, 6-naphthyridines. Bioorganic Med. Chem. Lett. 2001, 11, 103–105. [Google Scholar] [CrossRef]
- Chan, L.; Jin, H.; Stefanac, T.; Lavallée, J.-F.; Falardeau, G.; Wang, W. Discovery of 1, 6-naphthyridines as a novel class of potent and selective human cytomegalovirus inhibitors. J. Med. Chem. 1999, 42, 3023–3025. [Google Scholar] [CrossRef]
- Jordão, A.K.; Ferreira, V.F.; Souza, T.M.; de Souza Faria, G.G.; Machado, V.; Abrantes, J.L.; de Souza, M.C.; Cunha, A.C. Synthesis and anti-HSV-1 activity of new 1, 2, 3-triazole derivatives. Bioorganic Med. Chem. 2011, 19, 1860–1865. [Google Scholar] [CrossRef] [Green Version]
- Głowacka, I.E.; Balzarini, J.; Wróblewski, A.E. The synthesis, antiviral, cytostatic and cytotoxic evaluation of a new series of acyclonucleotide analogues with a 1, 2, 3-triazole linker. Eur. J. Med. Chem. 2013, 70, 703–722. [Google Scholar] [CrossRef]
- Głowacka, I.E.; Andrei, G.; Schols, D.; Snoeck, R.; Gawron, K. Design, Synthesis, and the Biological Evaluation of a New Series of Acyclic 1,2,3-Triazole Nucleosides. Arch. Der Pharm. 2017, 350, 1700166. [Google Scholar] [CrossRef] [Green Version]
- Cunha, A.C.; Ferreira, V.F.; Vaz, M.G.; Cassaro, R.A.A.; Resende, J.A.; Sacramento, C.Q.; Costa, J.; Abrantes, J.L.; Souza, T.M.L.; Jordão, A.K. Chemistry and anti-herpes simplex virus type 1 evaluation of 4-substituted-1 H-1, 2, 3-triazole-nitroxyl-linked hybrids. Mol. Divers. 2021, 25, 2035–2043. [Google Scholar] [CrossRef] [PubMed]
- Bernardino, A.M.; Castro, H.C.; Frugulhetti, I.C.; Loureiro, N.I.; Azevedo, A.R.; Pinheiro, L.C.; Souza, T.M.; Giongo, V.; Passamani, F.; Magalhaes, U.O. SAR of a series of anti-HSV-1 acridone derivatives, and a rational acridone-based design of a new anti-HSV-1 3H-benzo [b] pyrazolo [3, 4-h]-1, 6-naphthyridine series. Bioorganic Med. Chem. 2008, 16, 313–321. [Google Scholar] [CrossRef] [PubMed]
- Parcella, K.; Patel, M.; Tu, Y.; Eastman, K.; Peese, K.; Gillis, E.; Belema, M.; Dicker, I.B.; McAuliffe, B.; Ding, B. Scaffold modifications to the 4-(4, 4-dimethylpiperidinyl) 2, 6-dimethylpyridinyl class of HIV-1 allosteric integrase inhibitors. Bioorganic Med. Chem. 2022, 116833. [Google Scholar] [CrossRef]
- Karypidou, K.; Ribone, S.R.; Quevedo, M.A.; Persoons, L.; Pannecouque, C.; Helsen, C.; Claessens, F.; Dehaen, W. Synthesis, biological evaluation and molecular modeling of a novel series of fused 1, 2, 3-triazoles as potential anti-coronavirus agents. Bioorganic Med. Chem. Lett. 2018, 28, 3472–3476. [Google Scholar] [CrossRef] [PubMed]
- Hartwich, A.; Zdzienicka, N.; Schols, D.; Andrei, G.; Snoeck, R.; Głowacka, I.E. Design, synthesis and antiviral evaluation of novel acyclic phosphonate nucleotide analogs with triazolo [4, 5-b] pyridine, imidazo [4, 5-b] pyridine and imidazo [4, 5-b] pyridin-2 (3 H)-one systems. Nucl. Nucl. Nucleic Acids 2020, 39, 542–591. [Google Scholar] [CrossRef] [Green Version]
- Van Zundert, G.; Rodrigues, J.; Trellet, M.; Schmitz, C.; Kastritis, P.; Karaca, E.; Melquiond, A.; van Dijk, M.; De Vries, S.; Bonvin, A. The HADDOCK2. 2 web server: User-friendly integrative modeling of biomolecular complexes. J. Mol. Biol. 2016, 428, 720–725. [Google Scholar] [CrossRef] [Green Version]
- Jorgensen, W.L.; Maxwell, D.S.; Tirado-Rives, J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc. 1996, 118, 11225–11236. [Google Scholar] [CrossRef]
- Ortuso, F.; Langer, T.; Alcaro, S. GBPM: GRID-based pharmacophore model: Concept and application studies to protein–protein recognition. Bioinformatics 2006, 22, 1449–1455. [Google Scholar] [CrossRef] [Green Version]
- Ongaro, A.; Oselladore, E.; Memo, M.; Ribaudo, G.; Gianoncelli, A. Insight into the LFA-1/SARS-CoV-2 Orf7a complex by protein–protein docking, molecular dynamics, and MM-GBSA calculations. J. Chem. Inf. Model. 2021, 61, 2780–2787. [Google Scholar] [CrossRef]
- Eisenberg, R.; Atanasiu, D.; Cairns, T.; Gallagher, J.; Krummenacher, C.; Cohen, G. Herpes virus fusion and entry: A story with many characters. Viruses 2012, 4, 800–832. [Google Scholar] [CrossRef]
- Zhang, N.; Yan, J.; Lu, G.; Guo, Z.; Fan, Z.; Wang, J.; Shi, Y.; Qi, J.; Gao, G.F. Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell adhesion. Nat. Commun. 2011, 2, 577. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lazear, E.; Whitbeck, J.C.; Zuo, Y.; Carfí, A.; Cohen, G.H.; Eisenberg, R.J.; Krummenacher, C. Induction of conformational changes at the N-terminus of herpes simplex virus glycoprotein D upon binding to HVEM and nectin-1. Virology 2014, 448, 185–195. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Prejanò, M.; Romeo, I.; La Serra, M.A.; Russo, N.; Marino, T. Computational Study Reveals the Role of Water Molecules in the Inhibition Mechanism of LAT1 by 1, 2, 3-Dithiazoles. J. Chem. Inf. Model. 2021, 61, 5883–5892. [Google Scholar] [CrossRef] [PubMed]
- Schrödinger Release 2018-1: Desmond Molecular Dynamics System; D.E. Shaw Research, Maestro-Desmond Interoperability Tools; Schrödinger LLC: New York, NY, USA, 2018.
- Schrödinger Release 2018-1: Maestro; Schrödinger LLC: New York, NY, USA, 2018.
- Carfí, A.; Willis, S.H.; Whitbeck, J.C.; Krummenacher, C.; Cohen, G.H.; Eisenberg, R.J.; Wiley, D.C. Herpes simplex virus glycoprotein D bound to the human receptor HveA. Mol. Cell 2001, 8, 169–179. [Google Scholar] [CrossRef]
- Schrödinger Release 2018-1: Protein Preparation Wizard; Epik, 2019; Schrödinger LLC: New York, NY, USA, 2018.
- Jacobson, M.P.; Pincus, D.L.; Rapp, C.S.; Day, T.J.; Honig, B.; Shaw, D.E.; Friesner, R.A. A hierarchical approach to all-atom protein loop prediction. Proteins: Struct. Funct. Bioinform. 2004, 55, 351–367. [Google Scholar] [CrossRef] [Green Version]
- Greenwood, J.R.; Calkins, D.; Sullivan, A.P.; Shelley, J.C. Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution. J. Comput.-Aided Mol. Des. 2010, 24, 591–604. [Google Scholar] [CrossRef]
- Ortuso, F.; Mercatelli, D.; Guzzi, P.H.; Giorgi, F.M. Structural genetics of circulating variants affecting the SARS-CoV-2 spike/human ACE2 complex. J. Biomol. Struct. Dyn. 2022, 40, 6545–6555. [Google Scholar] [CrossRef]
- Hou, T.; Wang, J.; Li, Y.; Wang, W. Assessing the performance of the molecular mechanics/Poisson Boltzmann surface area and molecular mechanics/generalized Born surface area methods. II. The accuracy of ranking poses generated from docking. J. Comput. Chem. 2011, 32, 866–877. [Google Scholar] [CrossRef] [Green Version]
- Kopitz, H.; Cashman, D.A.; Pfeiffer-Marek, S.; Gohlke, H. Influence of the solvent representation on vibrational entropy calculations: Generalized born versus distance-dependent dielectric model. J. Comput. Chem. 2012, 33, 1004–1013. [Google Scholar] [CrossRef]
- Genheden, S.; Kuhn, O.; Mikulskis, P.; Hoffmann, D.; Ryde, U. The normal-mode entropy in the MM/GBSA method: Effect of system truncation, buffer region, and dielectric constant. J. Chem. Inf. Model. 2012, 52, 2079–2088. [Google Scholar] [CrossRef] [Green Version]
- Krummenacher, C.; Supekar, V.M.; Whitbeck, J.C.; Lazear, E.; Connolly, S.A.; Eisenberg, R.J.; Cohen, G.H.; Wiley, D.C.; Carfí, A. Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry. EMBO J. 2005, 24, 4144–4153. [Google Scholar] [CrossRef]
- Schrödinger Release 2018-1: LigPrep; Schrödinger LLC: New York, NY, USA, 2018.
- Prejanò, M.; Romeo, I.; Sgrizzi, L.; Russo, N.; Marino, T. Why hydroxy-proline improves the catalytic power of the peptidoglycan N-deacetylase enzyme: Insight from theory. Phys. Chem. Chem. Phys. 2019, 21, 23338–23345. [Google Scholar] [CrossRef] [PubMed]
- Maruca, A.; Ambrosio, F.A.; Lupia, A.; Romeo, I.; Rocca, R.; Moraca, F.; Talarico, C.; Bagetta, D.; Catalano, R.; Costa, G. Computer-based techniques for lead identification and optimization I: Basics. Phys. Sci. Rev. 2019, 4. [Google Scholar] [CrossRef]
- Lupia, A.; Moraca, F.; Bagetta, D.; Maruca, A.; Ambrosio, F.A.; Rocca, R.; Catalano, R.; Romeo, I.; Talarico, C.; Ortuso, F. Computer-based techniques for lead identification and optimization II: Advanced search methods. Phys. Sci. Rev. 2019, 5, 20180114. [Google Scholar] [CrossRef]
- Costa, G.; Rocca, R.; Moraca, F.; Talarico, C.; Romeo, I.; Ortuso, F.; Alcaro, S.; Artese, A. A Comparative Docking Strategy to Identify Polyphenolic Derivatives as Promising Antineoplastic Binders of G-quadruplex DNA c-myc and bcl-2 Sequences. Mol. Inform. 2016, 35, 391–402. [Google Scholar] [CrossRef]
- Friesner, R.A.; Murphy, R.B.; Repasky, M.P.; Frye, L.L.; Greenwood, J.R.; Halgren, T.A.; Sanschagrin, P.C.; Mainz, D.T. Extra Precision Glide: Docking and Scoring Incorporating a Model of Hydrophobic Enclosure for Protein-Ligand Complexes. J. Med. Chem. 2006, 49, 6177–6196. [Google Scholar] [CrossRef] [Green Version]
- Daina, A.; Michielin, O.; Zoete, V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 2017, 7, 42717. [Google Scholar] [CrossRef] [Green Version]
- Ferraro, M.; Colombo, G. Targeting difficult protein-protein interactions with plain and general computational approaches. Molecules 2018, 23, 2256. [Google Scholar] [CrossRef] [Green Version]
Cpd | R | R1 | Cpd | R | R1 |
---|---|---|---|---|---|
1 | H | Me | 10 | 3,4,5-(OMe)3 | Ph |
2 | H | Ph | 11 | 3,4,5-(OMe)3 | 2-OMe-Ph |
3 | H | 2-OMe-Ph | 12 | 3,4,5-(OMe)3 | 4-OMe-Ph |
4 | H | 4-OMe-Ph | 13 | H | COOEt |
5 | 4-OMe | Me | 14 | H | CH2OH |
6 | 4-OMe | Ph | 15 | 4-OMe | COOEt |
7 | 4-OMe | 2-OMe-Ph | 16 | 4-OMe | CH2OH |
8 | 4-OMe | 4-OMe-Ph | 17 | 3,4,5-(OMe)3 | COOEt |
9 | 3,4,5-(OMe)3 | Me | 18 | 3,4,5-(OMe)3 | CH2OH |
19 | H | 2-F-Ph | 55 | 4-Cl | 2-OMe-Ph |
20 | H | 2-Br-Ph | 56 | 4-Cl | 2-F-Ph |
21 | H | 2-Cl-Ph | 57 | 4-Cl | 2-Br-Ph |
22 | H | 2-NO2-Ph | 58 | 4-Cl | 2-Cl-Ph |
23 | H | 2-NH2-Ph | 59 | 4-Cl | 2-NO2-Ph |
24 | H | 2-CF3-Ph | 60 | 4-Cl | 2-NH2-Ph |
25 | H | 2,3-(OMe)2-Ph | 61 | 4-Cl | 2-CF3-Ph |
26 | H | 2,4-(OMe)2-Ph | 62 | 4-Cl | 2,3-(OMe)2-Ph |
27 | H | 2,5-(OMe)2-Ph | 63 | 4-Cl | 2,4-(OMe)2-Ph |
28 | H | 2-OMe-5-Cl-Ph | 64 | 4-Cl | 2,5-(OMe)2-Ph |
29 | H | 2-OMe-5-Br-Ph | 65 | 4-Cl | 2-OMe-5-Cl-Ph |
30 | 4-OMe | 2-F-Ph | 66 | 4-Cl | 2-OMe-5-Br-Ph |
31 | 4-OMe | 2-Br-Ph | 67 | 4-F | 4-OMe-Ph |
32 | 4-OMe | 2-Cl-Ph | 68 | 4-F | CH3 |
33 | 4-OMe | 2-NO2-Ph | 69 | 4-F | Ph |
34 | 4-OMe | 2-NH2-Ph | 70 | 4-F | 2-OMe-Ph |
35 | 4-OMe | 2-CF3-Ph | 71 | 4-F | 2-F-Ph |
36 | 4-OMe | 2,3-(OMe)2-Ph | 72 | 4-F | 2-Br-Ph |
37 | 4-OMe | 2,4-(OMe)2-Ph | 73 | 4-F | 2-Cl-Ph |
38 | 4-OMe | 2,5-(OMe)2-Ph | 74 | 4-F | 2-NO2-Ph |
39 | 4-OMe | 2-OMe-5-Cl-Ph | 75 | 4-F | 2-NH2-Ph |
40 | 4-OMe | 2-OMe-5-Br-Ph | 76 | 4-F | 2-CF3-Ph |
41 | 3,4,5-(OMe)3 | 2-F-Ph | 77 | 4-F | 2,3-(OMe)2-Ph |
42 | 3,4,5-(OMe)3 | 2-Br-Ph | 78 | 4-F | 2,4-(OMe)2-Ph |
43 | 3,4,5-(OMe)3 | 2-Cl-Ph | 79 | 4-F | 2,5-(OMe)2-Ph |
44 | 3,4,5-(OMe)3 | 2-NO2-Ph | 80 | 4-F | 2-OMe-5-Cl-Ph |
45 | 3,4,5-(OMe)3 | 2-NH2-Ph | 81 | 4-F | 2-OMe-5-Br-Ph |
46 | 3,4,5-(OMe)3 | 2-CF3-Ph | 82 | 4-Cl | COOEt |
47 | 3,4,5-(OMe)3 | 2,3-(OMe)2-Ph | 83 | 4-Cl | CH2OH |
48 | 3,4,5-(OMe)3 | 2,4-(OMe)2-Ph | 84 | 4-F | COOEt |
49 | 3,4,5-(OMe)3 | 2,5-(OMe)2-Ph | 85 | 4-F | CH2OH |
50 | 3,4,5-(OMe)3 | 2-OMe-5-Cl-Ph | |||
51 | 3,4,5-(OMe)3 | 2-OMe-5-Br-Ph | |||
52 | 4-Cl | 4-OMe-Ph | |||
53 | 4-Cl | CH3 | |||
54 | 4-Cl | Ph |
Complex | Cluster | HADDOCK Score | Cluster Size | Z-Score | BSA |
---|---|---|---|---|---|
gD-HVEM | 1 | −124.3 ± 5.6 | 96 | −2.1 | 2144.2 ± 59.6 |
2 | −89.1± 1.9 | 24 | −0.2 | 1939.7 ± 69.3 | |
3 | −97.5 ± 7.7 | 17 | −0.7 | 1925.6 ± 72.1 | |
4 | −93.7 ± 2.1 | 15 | −0.5 | 1965.3 ± 124.9 | |
5 | −54.1 ± 3.3 | 10 | 1.6 | 1401.2 ± 37.0 | |
6 | −82.2 ± 4.4 | 9 | 0.1 | 1543.9 ± 50.6 | |
7 | −76.3 ± 3.7 | 7 | 0.5 | 1864.7 ± 63.3 | |
8 | −70.1 ± 7.6 | 6 | 0.8 | 1652.0 ± 72.3 | |
9 | −75.7 ± 20.7 | 4 | 0.5 | 1701.5 ± 193.4 | |
gD-Nectin-1 | 1 | −146.0 ± 2.2 | 178 | −1.0 | 2107.6 ± 20.8 |
2 | −101.4 ± 3.0 | 20 | 1.0 | 1887 ± 108.6 |
gD-HVEM | gD-Nectin-1 | |||
---|---|---|---|---|
gD | HVEM | gD | Nectin-1 | |
Hydrogen bonds | Lys10 | Asp7 | Asp26 | Lys61 |
Ala12 | Tyr23 | Gln27 | Lys61 | |
Pro14 | Arg75 | Gln27 | Thr63 | |
Asn15 | Ser74 | Gln132 | Gln64 | |
Gly19 | Arg75 | Asp215 | Asn77 | |
Gln27 | Cys37 | Asp215 | Asn77 | |
Thr29 | Thr35 | Gly218 | Gln68 | |
Lys122 | Glu31 | Arg222 | Gly132 | |
Salt bridges | Lys10 | Asp7 | Arg222 | Glu125 |
Asp26 | Lys26 | Asp26 | Lys61 | |
Lys122 | Glu31 | Arg222 | Glu125 |
gD-HVEM | gD-Nectin-1 | ||||
---|---|---|---|---|---|
Residue | Average Score | Quartile | Residue | Average Score | Quartile |
Ala12 | −6.75 | Q1 | Arg222 | −1.80 | Q1 |
Asp13 | −2.08 | Q1 | Asp215 | −3.74 | Q1 |
Asn15 | −3.13 | Q1 | Asp26 | −1.01 | Q1 |
Asp26 | −1.97 | Q1 | Gln27 | −1.13 | Q1 |
Gln27 | −5.48 | Q1 | Gly218 | −0.97 | Q1 |
Thr29 | −10.00 | Q1 | Met219 | −1.28 | Q1 |
Gly33 | −1.21 | Q1 | Pro221 | −1.83 | Q1 |
Arg35 | −14.64 | Q1 | Ser200 | −1.85 | Q1 |
Lys10 | −0.21 | Q2 | Tyr38 | −1.09 | Q1 |
Lys122 | −0.47 | Q2 | Arg196 | −0.20 | Q2 |
Pro14 | −0.30 | Q2 | Arg64 | −0.83 | Q2 |
Lys186 | −0.20 | Q2 | Gln132 | −0.40 | Q2 |
Gly19 | −0.07 | Q2 | Leu25 | −0.44 | Q2 |
Leu257 | −0.12 | Q2 | Lys186 | −0.66 | Q2 |
Arg64 | −0.20 | Q2 | Pro23 | −0.23 | Q2 |
Ala7 | −0.67 | Q2 | Ser235 | −0.64 | Q2 |
Phe17 | −0.01 | Q3 | Tyr137 | −0.17 | Q2 |
Lys20 | −0.02 | Q3 | Arg184 | −0.04 | Q3 |
Leu25 | −0.03 | Q3 | Asn136 | −0.03 | Q3 |
Glu259 | −0.02 | Q3 | Asp139 | −0.16 | Q3 |
Asp30 | −0.06 | Q3 | Pro199 | −0.03 | Q3 |
Pro32 | −0.04 | Q3 | Ser140 | −0.04 | Q3 |
Ala5 | −0.04 | Q3 | Ser216 | −0.08 | Q3 |
Glu63 | −0.02 | Q3 | Tyr234 | −0.15 | Q3 |
Met11 | −0.01 | Q4 | Val24 | −0.05 | Q3 |
Arg18 | −0.01 | Q4 | Ala185 | −0.01 | Q4 |
Val24 | 0.00 | Q4 | Arg36 | −0.01 | Q4 |
Lys245 | −0.01 | Q4 | Asn227 | 0.00 | Q4 |
Ser258 | −0.01 | Q4 | Ile217 | −0.02 | Q4 |
Pro31 | 0.00 | Q4 | Lys190 | −0.02 | Q4 |
Val34 | −0.01 | Q4 | Phe223 | 0.00 | Q4 |
Leu4 | 0.00 | Q4 | Thr230 | −0.01 | Q4 |
Val231 | −0.02 | Q4 | |||
Val37 | −0.01 | Q4 |
Cpd | MW | H-Bond Acceptors | H-Bond Donors | LogP | TPSA | LogS |
---|---|---|---|---|---|---|
14 | 255.28 | 4 | 2 | 1.05 | 89.85 | −2.77 |
16 | 285.30 | 5 | 2 | 1.06 | 99.08 | −2.82 |
83 | 289.72 | 4 | 2 | 1.71 | 89.85 | −3.35 |
85 | 273.27 | 5 | 2 | 1.61 | 89.85 | −2.91 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Bivacqua, R.; Romeo, I.; Barreca, M.; Barraja, P.; Alcaro, S.; Montalbano, A. HSV-1 Glycoprotein D and Its Surface Receptors: Evaluation of Protein–Protein Interaction and Targeting by Triazole-Based Compounds through In Silico Approaches. Int. J. Mol. Sci. 2023, 24, 7092. https://doi.org/10.3390/ijms24087092
Bivacqua R, Romeo I, Barreca M, Barraja P, Alcaro S, Montalbano A. HSV-1 Glycoprotein D and Its Surface Receptors: Evaluation of Protein–Protein Interaction and Targeting by Triazole-Based Compounds through In Silico Approaches. International Journal of Molecular Sciences. 2023; 24(8):7092. https://doi.org/10.3390/ijms24087092
Chicago/Turabian StyleBivacqua, Roberta, Isabella Romeo, Marilia Barreca, Paola Barraja, Stefano Alcaro, and Alessandra Montalbano. 2023. "HSV-1 Glycoprotein D and Its Surface Receptors: Evaluation of Protein–Protein Interaction and Targeting by Triazole-Based Compounds through In Silico Approaches" International Journal of Molecular Sciences 24, no. 8: 7092. https://doi.org/10.3390/ijms24087092
APA StyleBivacqua, R., Romeo, I., Barreca, M., Barraja, P., Alcaro, S., & Montalbano, A. (2023). HSV-1 Glycoprotein D and Its Surface Receptors: Evaluation of Protein–Protein Interaction and Targeting by Triazole-Based Compounds through In Silico Approaches. International Journal of Molecular Sciences, 24(8), 7092. https://doi.org/10.3390/ijms24087092