{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:18:14Z","timestamp":1762543094569,"version":"build-2065373602"},"reference-count":93,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T00:00:00Z","timestamp":1565654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Belarusian Republican Foundation for Fundamental Research","award":["project X18K\u0418-002"],"award-info":[{"award-number":["project X18K\u0418-002"]}]},{"name":"the National Natural Science Foundation of China (NSFC) and the Belarusian Republican Foundation for Fundamental Research Cooperation and Exchange Program","award":["84630090"],"award-info":[{"award-number":["84630090"]}]},{"name":"the National Natural Science Foundation of China for Young Researchers","award":["81703567"],"award-info":[{"award-number":["81703567"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Despite recent progress in the development of novel potent HIV-1 entry\/fusion inhibitors, there are currently no licensed antiviral drugs based on inhibiting the critical interactions of the HIV-1 envelope gp120 protein with cellular receptor CD4. In this connection, studies on the design of new small-molecule compounds able to block the gp120-CD4 binding are still of great value. In this work, in silico design of drug-like compounds containing the moieties that make the ligand active towards gp120 was performed within the concept of click chemistry. Complexes of the designed molecules bound to gp120 were then generated by molecular docking and optimized using semiempirical quantum chemical method PM7. Finally, the binding affinity analysis of these ligand\/gp120 complexes was performed by molecular dynamic simulations and binding free energy calculations. As a result, five top-ranking compounds that mimic the key interactions of CD4 with gp120 and show the high binding affinity were identified as the most promising CD4-mimemic candidates. Taken together, the data obtained suggest that these compounds may serve as promising scaffolds for the development of novel, highly potent and broad anti-HIV-1 therapeutics.<\/jats:p>","DOI":"10.3390\/v11080746","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T03:59:26Z","timestamp":1565755166000},"page":"746","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["In Silico Identification of Novel Aromatic Compounds as Potential HIV-1 Entry Inhibitors Mimicking Cellular Receptor CD4"],"prefix":"10.3390","volume":"11","author":[{"given":"Alexander M.","family":"Andrianov","sequence":"first","affiliation":[{"name":"Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 220141 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grigory I.","family":"Nikolaev","sequence":"additional","affiliation":[{"name":"United Institute of Informatics Problems, National Academy of Sciences of Belarus, 220012 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri V.","family":"Kornoushenko","sequence":"additional","affiliation":[{"name":"Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 220141 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences, Fudan University, 131 Dong An Road, Fuxing Building, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shibo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences, Fudan University, 131 Dong An Road, Fuxing Building, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5970-4852","authenticated-orcid":false,"given":"Alexander V.","family":"Tuzikov","sequence":"additional","affiliation":[{"name":"United Institute of Informatics Problems, National Academy of Sciences of Belarus, 220012 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a006841","DOI":"10.1101\/cshperspect.a006841","article-title":"Origins of HIV and the AIDS pandemic","volume":"1","author":"Sharp","year":"2011","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_2","unstructured":"(2019, June 27). UNAIDS|AIDSinfo. Available online: http:\/\/aidsinfo.unaids.org\/."},{"key":"ref_3","unstructured":"(2019, June 27). U.S. Food and Drug Administration, Available online: https:\/\/www.fda.gov\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1021\/jm040158k","article-title":"New approaches toward anti-HIV chemotherapy","volume":"48","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0140-6736(07)61052-6","article-title":"HIV entry inhibitors","volume":"370","author":"Este","year":"2007","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.2174\/156802607781212239","article-title":"An update in the development of HIV entry inhibitors","volume":"7","author":"Rusconi","year":"2007","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S1359-6446(05)03550-6","article-title":"Progress in targeting HIV-1 entry","volume":"10","author":"Ryser","year":"2005","journal-title":"Drug Discov. Today"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.antiviral.2009.09.009","article-title":"Novel approaches to inhibiting HIV-1 replication","volume":"85","author":"Adamson","year":"2010","journal-title":"Antiviral Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3390\/v2020503","article-title":"HIV genetic diversity and drug resistance","volume":"2","author":"Santos","year":"2010","journal-title":"Viruses"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7589","DOI":"10.1128\/JVI.00302-14","article-title":"Mutations in HIV-1 reverse transcriptase affect the errors made in a single cycle of viral replication","volume":"88","author":"Abram","year":"2014","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"a007161","DOI":"10.1101\/cshperspect.a007161","article-title":"HIV-1 antiretroviral drug therapy","volume":"2","author":"Arts","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.hivar.2012.02.003","article-title":"Highly active antiretroviral therapy for treatment of HIV\/AIDS patients: Current status and future prospects and the Indian scenario","volume":"11","author":"Kumari","year":"2012","journal-title":"HIV Aids Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1080\/13543776.2017.1281249","article-title":"Small-molecule HIV-1 entry inhibitors targeting gp120 and gp41: A patent review (2010\u20132015)","volume":"27","author":"Li","year":"2017","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1097\/QAD.0000000000001415","article-title":"A novel HIV-1 gp41 tripartite model for rational design of HIV-1 fusion inhibitors with improved antiviral activity","volume":"31","author":"Su","year":"2017","journal-title":"AIDS"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"a006866","DOI":"10.1101\/cshperspect.a006866","article-title":"HIV: Cell binding and entry","volume":"2","author":"Wilen","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/31405","article-title":"Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody","volume":"393","author":"Kwong","year":"1998","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nrd1331","article-title":"Enfuvirtide: The first therapy to inhibit the entry of HIV-1 into host CD4 lymphocytes","volume":"3","author":"Matthews","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1086\/589289","article-title":"Reviews of anti-infective agents: Maraviroc: The first of a new class of antiretroviral agents","volume":"47","author":"MacArthur","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.virol.2005.06.008","article-title":"Identification of N-phenyl-N\u2019-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4","volume":"339","author":"Zhao","year":"2005","journal-title":"Virology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10973","DOI":"10.1021\/bi061193r","article-title":"Thermodynamics of binding of a low-molecular-weight CD4 mimetic to HIV-1 gp120","volume":"45","author":"Madani","year":"2006","journal-title":"Biochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1021\/jm300265j","article-title":"Structure-based design, synthesis, and characterization of dual hotspot small-molecule HIV-1 entry inhibitors","volume":"55","author":"Lalonde","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1021\/ml300407y","article-title":"Structure-based design and synthesis of an HIV-1 entry inhibitor exploiting X-ray and thermodynamic characterization","volume":"4","author":"Lalonde","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/j.str.2008.09.005","article-title":"Small-molecule CD4 mimics interact with a highly conserved pocket on HIV-1 gp120","volume":"16","author":"Madani","year":"2008","journal-title":"Structure"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5036","DOI":"10.1073\/pnas.0307953101","article-title":"Small molecule inhibitors of HIV-1 entry block receptor-induced conformational changes in the viral envelope glycoproteins","volume":"101","author":"Si","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5478","DOI":"10.1128\/AAC.03339-14","article-title":"Binding mode characterization of NBD series CD4-mimetic HIV-1 entry inhibitors by X-ray structure and resistance study","volume":"58","author":"Curreli","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4764","DOI":"10.1021\/jm3002247","article-title":"Design, synthesis and antiviral activity of entry inhibitors that target the CD4-binding site of HIV-1","volume":"55","author":"Curreli","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5853","DOI":"10.1016\/j.bmcl.2010.07.106","article-title":"CD4 mimics targeting the HIV entry mechanism and their hybrid molecules with a CXCR4 antagonist","volume":"20","author":"Narumi","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6735","DOI":"10.1016\/j.bmc.2011.09.045","article-title":"Small molecular CD4 mimics as HIV entry inhibitors","volume":"19","author":"Narumi","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1016\/j.bmc.2013.02.041","article-title":"CD4 mimics as HIV entry inhibitors: Lead optimization studies of the aromatic substituents","volume":"21","author":"Narumi","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.bmcl.2009.10.098","article-title":"CD4 mimics targeting the mechanism of HIV entry","volume":"20","author":"Yamada","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7884","DOI":"10.1016\/j.bmc.2013.10.005","article-title":"A CD4 mimic as an HIV entry inhibitor: Pharmacokinetics","volume":"21","author":"Hashimoto","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7558","DOI":"10.1128\/JVI.00227-10","article-title":"Enhanced exposure of human immunodeficiency virus type 1 primary isolate neutralization epitopes through binding of CD4 mimetic compounds","volume":"84","author":"Yoshimura","year":"2010","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1021\/ar4002735","article-title":"Structure-based design, synthesis and validation of CD4-mimetic small molecule inhibitors of HIV-1 entry: Conversion of a viral entry agonist to an antagonist","volume":"47","author":"Courter","year":"2014","journal-title":"Acc. Chem. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/cbdd.12075","article-title":"Optimization of CD4\/gp120 inhibitors by thermodynamic-guided alanine-scanning mutagenesis","volume":"81","author":"Liu","year":"2013","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6909","DOI":"10.1021\/acs.jmedchem.5b00709","article-title":"Structure-based design of a small molecule CD4-antagonist with broad spectrum anti-HIV-1 activity","volume":"58","author":"Curreli","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5033","DOI":"10.1021\/jm4002988","article-title":"Interfacial cavity filling to optimize CD4\u2013mimetic miniprotein interactions with HIV-1 surface glycoprotein","volume":"56","author":"Acharya","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1517\/14728222.2015.1010513","article-title":"HIV-1 gp120 as a therapeutic target: Navigating a moving labyrinth","volume":"19","author":"Acharya","year":"2015","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3124","DOI":"10.1021\/acs.jmedchem.7b00179","article-title":"Synthesis, antiviral potency, in vitro ADMET, and X-ray structure of potent CD4 mimics as entry inhibitors that target the Phe43 cavity of HIV-1 gp120","volume":"60","author":"Curreli","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.ejmech.2018.04.062","article-title":"Structure-based lead optimization to improve antiviral potency and ADMET properties of phenyl-1H-pyrrole-carboxamide entry inhibitors targeted to HIV-1 gp120","volume":"154","author":"Curreli","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5663","DOI":"10.1073\/pnas.1112391109","article-title":"Unliganded HIV-1 gp120 core structures assume the CD4-bound conformation with regulation by quaternary interactions and variable loops","volume":"109","author":"Kwon","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kwon, Y.D., Lalonde, J.M., Yang, Y., Elban, M.A., Sugawara, A., Courter, J.R., Jones, D.M., Smith, A.B., Debnath, A.K., and Kwong, P.D. (2014). Crystal structures of HIV-1 gp120 envelope glycoprotein in complex with NBD analogues that target the CD4-binding site. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085940"},{"key":"ref_42","first-page":"3","article-title":"In-silico drug design: An approach which revolutionarised the drug discovery process","volume":"1","author":"Wadood","year":"2013","journal-title":"OA Drug Des. Deliv."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1124\/pr.112.007336","article-title":"Computational Methods in Drug Discovery","volume":"66","author":"Sliwoski","year":"2014","journal-title":"Pharmacol. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.2174\/1568026614666140929153812","article-title":"Recent advances in computer-aided drug design as applied to anti-influenza drug discovery","volume":"14","author":"Mallipeddi","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.3762\/bjoc.12.267","article-title":"Computational methods in drug discovery","volume":"12","author":"Leelananda","year":"2016","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.csbj.2016.04.004","article-title":"Computational approaches in target identification and drug discovery","volume":"14","author":"Katsila","year":"2016","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.csbj.2016.09.002","article-title":"The promises of quantitative systems pharmacology modelling for drug development","volume":"14","author":"Chelliah","year":"2016","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/nature03197","article-title":"Virtual screening of chemical libraries","volume":"432","author":"Shoichet","year":"2004","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.4155\/fmc-2018-0076","article-title":"A review of ligand-based virtual screening web tools and screening algorithms in large molecular databases in the age of big data","volume":"10","year":"2018","journal-title":"Future Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3389\/fchem.2018.00138","article-title":"Reverse screening methods to search for the protein targets of chemopreventive compounds","volume":"6","author":"Huang","year":"2018","journal-title":"Front. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1002\/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5","article-title":"Click chemistry: Diverse chemical function from a few good reactions","volume":"40","author":"Kolb","year":"2001","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1039\/B613014N","article-title":"The growing applications of click chemistry","volume":"36","author":"Moses","year":"2007","journal-title":"Chem. Soc. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1007\/s11095-008-9616-1","article-title":"Click chemistry, a powerful tool for pharmaceutical sciences","volume":"10","author":"Hein","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4905","DOI":"10.1021\/cr200409f","article-title":"Click chemistry for drug development and diverse chemical\u2013biology applications","volume":"113","author":"Thirumurugan","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Durrant, J.D., and McCammon, J.A. (2012). AutoClickChem: Click chemistry in silico. PLoS Comput. Biol., 8.","DOI":"10.1371\/journal.pcbi.1002397"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1021\/ci3001277","article-title":"ZINC: A free tool to discover chemistry for biology","volume":"52","author":"Irwin","year":"2012","journal-title":"J. Chem. Inf. Model."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1021\/ci500588j","article-title":"DataWarrior: An open-source program for chemistry aware data visualization and analysis","volume":"55","author":"Sander","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1109\/TCBB.2012.82","article-title":"QuickVina: Accelerating AutoDock Vina using gradient-based heuristics for global optimization","volume":"9","author":"Handoko","year":"2012","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinform."},{"key":"ref_60","unstructured":"(2019, June 27). Open Babel. Available online: http:\/\/openbabel.org\/wiki\/Main_Page."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"10024","DOI":"10.1021\/ja00051a040","article-title":"UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations","volume":"114","author":"Rappe","year":"1992","journal-title":"J. Am. Chem. Soc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00894-012-1667-x","article-title":"Optimization of parameters for semiempirical methods VI: More modifications to the NDDO approximations and re-optimization of parameters","volume":"19","author":"Stewart","year":"2013","journal-title":"J. Mol. Model."},{"key":"ref_63","unstructured":"(2019, June 27). OpenMOPAC. Available online: http:\/\/OpenMOPAC.net."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1039\/P29930000799","article-title":"COSMO: A new approach to dielectric screening in solvents with explicit expressions for the screening energy and its gradient","volume":"2","author":"Klamt","year":"1993","journal-title":"J. Chem. Soc. Perkin Trans. 2"},{"key":"ref_65","unstructured":"Klamt, A. (2005). COSMO-RS: From Quantum Chemistry to Fluid Phase Thermodynamics and Drug Design, Elsevier. [1st ed.]."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4220","DOI":"10.1021\/acs.jctc.5b00601","article-title":"A comprehensive comparison of the IEFPCM and SS(V)PE continuum solvation methods with the COSMO approach","volume":"11","author":"Klamt","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1021\/ct300473g","article-title":"Trust region minimization of orbital localization functions","volume":"8","author":"Jansik","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5365","DOI":"10.1021\/ct400793q","article-title":"Unitary optimization of localized molecular orbitals","volume":"9","author":"Lehtola","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.jmgm.2011.01.004","article-title":"Binana: A novel algorithm for ligand-binding characterization","volume":"29","author":"Durrant","year":"2011","journal-title":"J. Mol. Graph. Model."},{"key":"ref_70","first-page":"16051","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"13","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1006\/jmbi.1994.1334","article-title":"Satisfying hydrogen bonding potential in proteins","volume":"238","author":"McDonald","year":"1994","journal-title":"J. Mol. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1021\/ci2003889","article-title":"NNScore 2.0: A neural-network receptor-ligand scoring function","volume":"51","author":"Durrant","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"ref_73","unstructured":"Case, D.A., Darden, T.A., Cheatham, T.E., Simmerling, C.L., Wang, J., and Duke, R.E. (2010). AMBER 11, University of California."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and testing of a general Amber force field","volume":"25","author":"Wang","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of the Cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes","volume":"23","author":"Ryckaert","year":"1977","journal-title":"J. Comput. Phys."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle mesh Ewald method","volume":"103","author":"Essmann","year":"1995","journal-title":"J. Chem. Phys."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"16719","DOI":"10.1039\/C4CP01388C","article-title":"Assessing the performance of MM\/PBSA and MM\/GBSA methods. 4. Accuracies of MM\/PBSA and MM\/GBSA methodologies evaluated by various simulation protocols using PDBbind data set","volume":"16","author":"Sun","year":"2014","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"8408","DOI":"10.1021\/jp404160y","article-title":"Assessing the performance of MM\/PBSA and MM\/GBSA methods. 3. The impact of force fields and ligand charge models","volume":"117","author":"Xu","year":"2013","journal-title":"J. Phys. Chem. B"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"22035","DOI":"10.1039\/C4CP03179B","article-title":"Assessing the performance of MM\/PBSA and MM\/GBSA methods. 5. Improved docking performance using high solute dielectric constant MM\/GBSA and MM\/PBSA rescoring","volume":"16","author":"Sun","year":"2014","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1002\/prot.22711","article-title":"Improved side-chain torsion potentials for the Amber ff99SB protein force field","volume":"78","author":"Piana","year":"2010","journal-title":"Proteins"},{"key":"ref_82","unstructured":"(2019, June 27). Drug Likeness Tool (DruLiTo), Available online: http:\/\/www.niper.gov.in\/pi_dev_tools\/DruLiToWeb\/."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1084\/jem.176.2.507","article-title":"The human immunodeficiency virus-gp120 binding-site on CD4\u2014Delineation by quantitative equilibrium and kinetic binding studies of mutants in conjunction with a high-resolution CD4 atomic-structure","volume":"176","author":"Moebius","year":"1992","journal-title":"J. Exp. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5701","DOI":"10.1128\/jvi.64.12.5701-5707.1990","article-title":"Identification of individual human-immunodeficiency-virus type-1 gp120 amino-acids important for CD4 receptor-binding","volume":"64","author":"Olshevsky","year":"1990","journal-title":"J. Virol."},{"key":"ref_85","first-page":"1","article-title":"Combined docking with classical force field and quantum chemical semiempirical method PM7","volume":"5","author":"Sulimov","year":"2017","journal-title":"Adv. Bioinform."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4179","DOI":"10.1074\/jbc.M808500200","article-title":"Thermodynamic Analysis Reveals a Temperature-dependent Change in the Catalytic Mechanism of Bacillus stearothermophilus Tyrosyl-tRNA Synthetase","volume":"284","author":"Sharma","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"9026","DOI":"10.1073\/pnas.97.16.9026","article-title":"Energetics of the HIV gp120-CD4 binding reaction","volume":"97","author":"Myszka","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/nsmb.2351","article-title":"Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer","volume":"19","author":"Mao","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"12438","DOI":"10.1073\/pnas.1307382110","article-title":"Molecular architecture of the uncleaved HIV-1 envelope glycoprotein trimer","volume":"110","author":"Mao","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Tran, E.E.H., Borgnia, M.J., Kuybeda, O., Schauder, D.M., Bartesaghi, A., Frank, G.A., Sapiro, G., Milne, J.L.S., and Subramaniam, S. (2012). Structural mechanism of trimeric HIV-1 envelope glycoprotein activation. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002797"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1021\/acs.jcim.6b00393","article-title":"Computational evaluation of HIV-1 gp120 conformations of soluble trimeric gp140 structures as targets for de novo docking of first- and second-generation small-molecule CD4 mimics","volume":"56","author":"Moraca","year":"2016","journal-title":"J. Chem. Inf. Model."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.bmc.2010.11.049","article-title":"Design, synthesis and biological evaluation of small molecule inhibitors of CD4-gp120 binding based on virtual screening","volume":"19","author":"LaLonde","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1126\/science.1245625","article-title":"Crystal structure of a soluble cleaved HIV-1 envelope trimer","volume":"342","author":"Julien","year":"2013","journal-title":"Science"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/8\/746\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:10:45Z","timestamp":1760188245000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/8\/746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,13]]},"references-count":93,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["v11080746"],"URL":"https:\/\/doi.org\/10.3390\/v11080746","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2019,8,13]]}}}