{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T11:26:49Z","timestamp":1762342009697,"version":"build-2065373602"},"reference-count":101,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T00:00:00Z","timestamp":1674864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UCSM","award":["24150-R-2017VRINV","25175-R-2018VRINV","23824-R-2016VRINV"],"award-info":[{"award-number":["24150-R-2017VRINV","25175-R-2018VRINV","23824-R-2016VRINV"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The increasing emergence of Mycobacterium tuberculosis (Mtb) strains resistant to traditional anti-tuberculosis drugs has alarmed health services worldwide. The search for new therapeutic targets and effective drugs that counteract the virulence and multiplication of Mtb represents a challenge for the scientific community. Several studies have considered the erp gene a possible therapeutic target in the last two decades, since its disruption negatively impacts Mtb multiplication. This gene encodes the exported repetitive protein (Erp), which is located in the cell wall of Mtb. In vitro studies have shown that the Erp protein interacts with two putative membrane proteins, Rv1417 and Rv2617c, and the impairment of their interactions can decrease Mtb replication. In this study, we present five nicotine analogs that can inhibit the formation of heterodimers and trimers between these proteins. Through DFT calculations, molecular dynamics, docking, and other advanced in silico techniques, we have analyzed the molecular complexes, and show the effect these compounds have on protein interactions. The results show that four of these analogs can be possible candidates to counteract the pathogenicity of Mtb. This study aims to combine research on the Erp protein as a therapeutic target in the search for new drugs that serve to create new therapies against tuberculosis disease.<\/jats:p>","DOI":"10.3390\/biom13020248","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T04:31:27Z","timestamp":1675053087000},"page":"248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Study of the Rv1417 and Rv2617c Membrane Proteins and Their Interactions with Nicotine Derivatives as Potential Inhibitors of Erp Virulence-Associated Factor in Mycobacterium tuberculosis: An In Silico Approach"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2921-5681","authenticated-orcid":false,"given":"Jorge Alberto","family":"Aguilar-Pineda","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ingenier\u00eda Molecular\u2014CIIM, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04013, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9305-7003","authenticated-orcid":false,"given":"Camilo","family":"Febres-Molina","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ingenier\u00eda Molecular\u2014CIIM, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04013, Peru"},{"name":"Doctorado en Fisicoqu\u00edmica Molecular, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago de Chile 8370134, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9871-3134","authenticated-orcid":false,"given":"Cinthia C.","family":"Cordova-Barrios","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Farmac\u00e9uticas, Bioqu\u00edmicas y Biotecnol\u00f3gicas, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04013, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4272-6948","authenticated-orcid":false,"given":"Lizbeth M.","family":"Campos-Olaz\u00e1val","sequence":"additional","affiliation":[{"name":"Facultad de Arquitectura e Ingenier\u00eda Civil y del Ambiente, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04013, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6030-6296","authenticated-orcid":false,"given":"Bruno A.","family":"Del-Carpio-Martinez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ingenier\u00eda Molecular\u2014CIIM, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04013, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9222-2983","authenticated-orcid":false,"given":"Flor","family":"Ayqui-Cueva","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ingenier\u00eda Molecular\u2014CIIM, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04013, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7277-7925","authenticated-orcid":false,"given":"Pamela L.","family":"Gamero-Begazo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ingenier\u00eda Molecular\u2014CIIM, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04013, Peru"},{"name":"Doctorado en Fisicoqu\u00edmica Molecular, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago de Chile 8370134, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6539-1207","authenticated-orcid":false,"given":"Badhin","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ingenier\u00eda Molecular\u2014CIIM, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04013, Peru"},{"name":"Departamento de Ciencias Farmac\u00e9uticas, Bioqu\u00edmicas y Biotecnol\u00f3gicas, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04013, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2001718","DOI":"10.1183\/13993003.01718-2020","article-title":"The potential impact of COVID-19-related disruption on tuberculosis burden","volume":"56","author":"McQuaid","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.medcli.2021.04.004","article-title":"Diabetes y tuberculosis: Una sindemia complicada por la COVID-19","volume":"157","year":"2021","journal-title":"Med. Cl\u00ednica"},{"key":"ref_3","unstructured":"W.H.O. (2021). Global Tuberculosis Report 2021, World Health Organization."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3349\/ymj.2009.50.1.1","article-title":"Macrophage apoptosis in tuberculosis","volume":"50","author":"Lee","year":"2009","journal-title":"Yonsei Med J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.chom.2011.11.012","article-title":"Mycobacterium tuberculosis inhibits neutrophil apoptosis, leading to delayed activation of naive CD4 T cells","volume":"11","author":"Blomgran","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3506","DOI":"10.4049\/jimmunol.1701448","article-title":"MicroRNA-27b modulates inflammatory response and apoptosis during Mycobacterium tuberculosis infection","volume":"200","author":"Liang","year":"2018","journal-title":"J. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1164\/rccm.200402-140OE","article-title":"A century of tuberculosis","volume":"169","author":"Murray","year":"2004","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1001\/jama.1941.02820390008003","article-title":"Treatment of Experimental Tuberculosis: Use of Sodium P, P\u2019-Diaminodiphenylsulfone-N, N\u2019-Didextrose Sulfonate (Promin) with Notes on Some Toxic Effects Observed in Man","volume":"117","author":"Hinshaw","year":"1941","journal-title":"J. Am. Med Assoc."},{"key":"ref_9","unstructured":"(2022, March 25). Tuberculosis. Available online: https:\/\/www.who.int\/es\/news-room\/fact-sheets\/detail\/tuberculosis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1183\/09031936.00214014","article-title":"Towards tuberculosis elimination: An action framework for low-incidence countries","volume":"45","author":"Migliori","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1056\/NEJMra1413919","article-title":"Treatment of tuberculosis","volume":"373","author":"Horsburgh","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_12","first-page":"729","article-title":"The diagnosis and treatment of tuberculosis","volume":"116","author":"Rademacher","year":"2019","journal-title":"Dtsch. Aerzteblatt Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.ejmech.2018.03.020","article-title":"Drug discovery in tuberculosis. New drug targets and antimycobacterial agents","volume":"150","author":"Moreira","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Gibson, S.E., Harrison, J., and Cox, J.A. (2018). Modelling a silent epidemic: A review of the in vitro models of latent tuberculosis. Pathogens, 7.","DOI":"10.20944\/preprints201810.0701.v1"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S85","DOI":"10.1016\/j.ijid.2020.02.017","article-title":"Towards more accurate 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging in active and latent tuberculosis","volume":"92","author":"Priftakis","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_16","unstructured":"Pan American Health Organization (2021). Tuberculosis in the Americas. Regional Report 2020, Pan American Health Organization."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Iacobino, A., Fattorini, L., and Giannoni, F. (2020). Drug-resistant tuberculosis 2020: Where we stand. Appl. Sci., 10.","DOI":"10.3390\/app10062153"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Al-Mutairi, N.M., Ahmad, S., Mokaddas, E., Eldeen, H.S., and Joseph, S. (2019). Occurrence of disputed rpoB mutations among Mycobacterium tuberculosis isolates phenotypically susceptible to rifampicin in a country with a low incidence of multidrug-resistant tuberculosis. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-018-3638-z"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/ddr.21498","article-title":"Bedaquiline and delamanid in the treatment of multidrug-resistant tuberculosis: Promising but challenging","volume":"80","author":"Li","year":"2019","journal-title":"Drug Dev. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"123237","DOI":"10.1016\/j.physa.2019.123237","article-title":"Analysis of tuberculosis model with saturated incidence rate and optimal control","volume":"540","author":"Baba","year":"2020","journal-title":"Phys. A Stat. Mech. Its Appl."},{"key":"ref_21","unstructured":"World Health Organization (2020). Global Tuberculosis Report 2020, World Health Organization."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S96","DOI":"10.1016\/j.ijid.2021.02.067","article-title":"Accelerating development of new shorter TB treatment regimens in anticipation of a resurgence of multi-drug resistant TB due to the COVID-19 pandemic","volume":"113","author":"Tiberi","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ijtb.2021.04.008","article-title":"Drug resistant tuberculosis: Current scenario and impending challenges","volume":"69","author":"Dewhare","year":"2021","journal-title":"Indian J. Tuberc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/s41429-019-0205-9","article-title":"Strategies in anti-Mycobacterium tuberculosis drug discovery based on phenotypic screening","volume":"72","author":"Grzelak","year":"2019","journal-title":"J. Antibiot."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.trsl.2020.03.007","article-title":"New tuberculosis drug targets, their inhibitors, and potential therapeutic impact","volume":"220","author":"Shetye","year":"2020","journal-title":"Transl. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Macalino, S.J.Y., Billones, J.B., Organo, V.G., and Carrillo, M.C.O. (2020). In silico strategies in tuberculosis drug discovery. Molecules, 25.","DOI":"10.3390\/molecules25030665"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6181","DOI":"10.1007\/s11033-021-06611-7","article-title":"Latent tuberculosis: Interaction of virulence factors in Mycobacterium tuberculosis","volume":"48","author":"Sundararajan","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4161\/viru.22329","article-title":"Virulence factors of the Mycobacterium tuberculosis complex","volume":"4","author":"Forrellad","year":"2013","journal-title":"Virulence"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1099\/13500872-141-9-2123","article-title":"Characterization of the Mycobacterium tuberculosis erp gene encoding a potential cell surface protein with repetitive structures","volume":"141","author":"Berthet","year":"1995","journal-title":"Microbiology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1128\/JB.00120-16","article-title":"Interaction of Erp protein of Mycobacterium tuberculosis with Rv2212 enhances intracellular survival of Mycobacterium smegmatis","volume":"198","author":"Ganaie","year":"2016","journal-title":"J. Bacteriol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1556\/030.65.2018.048","article-title":"Immune responses elicited by the recombinant Erp, HspR, LppX, MmaA4, and OmpA proteins from Mycobacterium tuberculosis in mice","volume":"66","author":"Okay","year":"2019","journal-title":"Acta Microbiol. Immunol. Hung."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5192","DOI":"10.1016\/j.vaccine.2014.07.047","article-title":"Hyper-attenuated MTBVAC erp mutant protects against tuberculosis in mice","volume":"32","author":"Solans","year":"2014","journal-title":"Vaccine"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Klepp, L.I., Soria, M., Blanco, F.C., Bianco, M.V., Santangelo, M.P., Cataldi, A.A., and Bigi, F. (2009). Identification of two proteins that interact with the Erp virulence factor from Mycobacterium tuberculosis by using the bacterial two-hybrid system. BMC Mol. Biol., 10.","DOI":"10.1186\/1471-2199-10-3"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Paco-Chipana, M., Febres-Molina, C., Aguilar-Pineda, J.A., and G\u00f3mez, B. (2022). Novel In Silico Insights into Rv1417 and Rv2617c as Potential Protein Targets: The Importance of the Medium on the Structural Interactions with Exported Repetitive Protein (Erp) of Mycobacterium tuberculosis. Polymers, 14.","DOI":"10.3390\/polym14132577"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1080\/21505594.2019.1693714","article-title":"Rv2617c and P36 are virulence factors of pathogenic mycobacteria involved in resistance to oxidative stress","volume":"10","author":"Forrellad","year":"2019","journal-title":"Virulence"},{"key":"ref_36","first-page":"115","article-title":"Endogenous and exogenous KdpF peptide increases susceptibility of Mycobacterium bovis BCG to nitrosative stress and reduces intramacrophage replication","volume":"7","author":"Molle","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"102266","DOI":"10.1016\/j.tube.2022.102266","article-title":"Bedaquiline resistant Mycobacterium tuberculosis clinical isolates with and without rv0678 mutations have similar growth patterns under varying BDQ drug pressure","volume":"137","author":"Saeed","year":"2022","journal-title":"Tuberculosis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3998\/ark.5550190.0008.f18","article-title":"Evaluation of anti-tubercular activity of nicotinic and isoniazid analogues","volume":"15","author":"Lourenco","year":"2007","journal-title":"Arkivoc"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.bmc.2018.11.017","article-title":"Synthesis and characterization of pyridoxine, nicotine and nicotinamide salts of dithiophosphoric acids as antibacterial agents against resistant wound infection","volume":"27","author":"Dang","year":"2019","journal-title":"Bioorganic Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1001\/jama.1952.03680100015006","article-title":"Treatment of pulmonary tuberculosis with hydrazide derivatives of isonicotinic acid","volume":"150","author":"Selikoff","year":"1952","journal-title":"J. Am. Med. Assoc."},{"key":"ref_41","first-page":"899","article-title":"Ineffectiveness of nicotinamide and isoniazid in the treatment of pulmonary tuberculosis","volume":"83","author":"Jordahl","year":"1961","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1086\/367544","article-title":"Nicotinamide: An oral antimicrobial agent with activity against both Mycobacterium tuberculosis and human immunodeficiency virus","volume":"36","author":"Murray","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e202104425","DOI":"10.1002\/slct.202104425","article-title":"Research Progress in the Pharmacological Effects and Synthesis of Nicotine","volume":"7","author":"Ye","year":"2022","journal-title":"ChemistrySelect"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/j.bmc.2016.02.035","article-title":"Novel nicotine analogues with potential anti-mycobacterial activity","volume":"24","author":"Gandhi","year":"2016","journal-title":"Bioorganic Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"100647","DOI":"10.1016\/j.cdc.2021.100647","article-title":"Docking and molecular dynamic study of isoniazid derivatives as anti-tuberculosis drug candidate","volume":"32","author":"Mardianingrum","year":"2021","journal-title":"Chem. Data Collect."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ijtb.2016.11.012","article-title":"Pyridines: Multidrug-resistant tuberculosis (MDR-TB) inhibitors","volume":"64","author":"Chaudhari","year":"2017","journal-title":"Indian J. Tuberc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"105374","DOI":"10.1016\/j.ejps.2020.105374","article-title":"Pyridine and quinoline molecules as crucial protagonists in the never-stopping discovery of new agents against tuberculosis","volume":"151","author":"Kouznetsov","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold Protein Structure Database: Massively expanding the structural coverage of protein-sequence space with high-accuracy models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_50","unstructured":"(2022, June 05). Exported Repetitive Protein, Accession Code AF-P9WIQ7-F1. Available online: https:\/\/alphafold.ebi.ac.uk\/entry\/P9WIQ7."},{"key":"ref_51","unstructured":"(2022, June 05). Uncharacterized Protein Rv1417, Accession Code AF-P9WLY1-F1. Available online: https:\/\/alphafold.ebi.ac.uk\/entry\/P9WLY1."},{"key":"ref_52","unstructured":"(2022, June 05). Probable Transmembrane Protein, Accession Code AF-I6XER9-F1. Available online: https:\/\/alphafold.ebi.ac.uk\/entry\/I6XER9."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.ymeth.2006.08.006","article-title":"Setting up and running molecular dynamics simulations of membrane proteins","volume":"41","author":"Kandt","year":"2007","journal-title":"Methods"},{"key":"ref_54","unstructured":"(2021, September 20). Exported Repetitive Protein, Accession Code P9WIQ7. Available online: https:\/\/www.uniprot.org\/uniprot\/P9WIQ7."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"W582","DOI":"10.1093\/nar\/gkq383","article-title":"Fpocket: Online tools for protein ensemble pocket detection and tracking","volume":"38","author":"Schmidtke","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2. 0: New docking methods, expanded force field, and python bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1002\/jcc.26011","article-title":"More bang for your buck: Improved use of GPU nodes for GROMACS 2018","volume":"40","author":"Kutzner","year":"2019","journal-title":"J. Comput. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11225","DOI":"10.1021\/ja9621760","article-title":"Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids","volume":"118","author":"Jorgensen","year":"1996","journal-title":"J. Am. Chem. Soc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6474","DOI":"10.1021\/jp003919d","article-title":"Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides","volume":"105","author":"Kaminski","year":"2001","journal-title":"J. Phys. Chem. B"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4871","DOI":"10.1063\/1.472323","article-title":"Molecular dynamics simulations of a fully hydrated dipalmitoylphosphatidylcholine bilayer with different macroscopic boundary conditions and parameters","volume":"105","author":"Tieleman","year":"1996","journal-title":"J. Chem. Phys."},{"key":"ref_63","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_64","doi-asserted-by":"crossref","first-page":"D1388","DOI":"10.1093\/nar\/gkaa971","article-title":"PubChem in 2021: New data content and improved web interfaces","volume":"49","author":"Kim","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_65","unstructured":"Dennington, R., Keith, T.A., and Millam, J.M. (2016). GaussView 6.0."},{"key":"ref_66","unstructured":"Frisch, M., Trucks, G., Schlegel, H., Scuseria, G., Robb, M., Cheeseman, J., Scalmani, G., Barone, V., Petersson, G., and Nakatsuji, H. (2016). Gaussian 16, Gaussian, Inc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cplett.2004.06.011","article-title":"A new hybrid exchange\u2013correlation functional using the Coulomb-attenuating method (CAM-B3LYP)","volume":"393","author":"Yanai","year":"2004","journal-title":"Chem. Phys. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5829","DOI":"10.1063\/1.467146","article-title":"Fully optimized contracted Gaussian basis sets of triple zeta valence quality for atoms Li to Kr","volume":"100","author":"Huber","year":"1994","journal-title":"J. Chem. Phys."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/BF00549096","article-title":"Bonded-atom fragments for describing molecular charge densities","volume":"44","author":"Hirshfeld","year":"1977","journal-title":"Theor. Chim. Acta"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/jcc.540080430","article-title":"Some methods and applications of electron density distribution analysis","volume":"8","author":"Ritchie","year":"1987","journal-title":"J. Comput. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"W331","DOI":"10.1093\/nar\/gkx312","article-title":"LigParGen web server: An automatic OPLS-AA parameter generator for organic ligands","volume":"45","author":"Dodda","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Duhovny, D., Nussinov, R., and Wolfson, H.J. (2002, January 17\u201321). Efficient unbound docking of rigid molecules. Proceedings of the International Workshop on Algorithms in Bioinformatics, Rome, Italy.","DOI":"10.1007\/3-540-45784-4_14"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"W363","DOI":"10.1093\/nar\/gki481","article-title":"PatchDock and SymmDock: Servers for rigid and symmetric docking","volume":"33","author":"Inbar","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/prot.21495","article-title":"FireDock: Fast interaction refinement in molecular docking","volume":"69","author":"Andrusier","year":"2007","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"W229","DOI":"10.1093\/nar\/gkn186","article-title":"FireDock: A web server for fast interaction refinement in molecular docking","volume":"36","author":"Mashiach","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/minf.201100135","article-title":"Free energy calculations by the molecular mechanics Poisson- Boltzmann surface area method","volume":"31","author":"Homeyer","year":"2012","journal-title":"Mol. Informatics"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1021\/ci500020m","article-title":"g_mmpbsa A GROMACS tool for high-throughput MM-PBSA calculations","volume":"54","author":"Kumari","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_80","unstructured":"Turner, P., and Grace, X. (2005). Center for Coastal and Land-Margin Research, Version 5.1.19."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/protein\/8.2.127","article-title":"LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions","volume":"8","author":"Wallace","year":"1995","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"10037","DOI":"10.1073\/pnas.181342398","article-title":"Electrostatics of nanosystems: Application to microtubules and the ribosome","volume":"98","author":"Baker","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"W665","DOI":"10.1093\/nar\/gkh381","article-title":"PDB2PQR: An automated pipeline for the setup of Poisson\u2013Boltzmann electrostatics calculations","volume":"32","author":"Dolinsky","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_84","unstructured":"Inc., W. (2020). Mathematica."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"W5","DOI":"10.1093\/nar\/gkab255","article-title":"ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties","volume":"49","author":"Xiong","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Aguilar-Pineda, J.A., Albaghdadi, M., Jiang, W., Vera-Lopez, K.J., Nieto-Montesinos, R., Alvarez, K.L.F., Davila Del-Carpio, G., G\u00f3mez, B., Lindsay, M.E., and Malhotra, R. (2021). Structural and functional analysis of female sex hormones against SARS-CoV-2 cell entry. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111508"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Aguilar-Pineda, J.A., Paco-Coralla, S.G., Febres-Molina, C., Gamero-Begazo, P.L., Shrivastava, P., Vera-L\u00f3pez, K.J., Davila-Del-Carpio, G., L\u00f3pez-C, P., G\u00f3mez, B., and Lino Cardenas, C.L. (2022). In Silico Analysis of the Antagonist Effect of Enoxaparin on the ApoE4\u2013Amyloid-Beta (A \u03b2) Complex at Different pH Conditions. Biomolecules, 12.","DOI":"10.3390\/biom12040499"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Febres-Molina, C., Aguilar-Pineda, J.A., Gamero-Begazo, P.L., Barazorda-Ccahuana, H.L., Valencia, D.E., Vera-L\u00f3pez, K.J., Davila-Del-Carpio, G., and G\u00f3mez, B. (2021). Structural and Energetic Affinity of Annocatacin B with ND1 Subunit of the Human Mitochondrial Respiratory Complex I as a Potential Inhibitor: An In Silico Comparison Study with the Known Inhibitor Rotenone. Polymers, 13.","DOI":"10.3390\/polym13111840"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s10822-015-9864-1","article-title":"A consistent S-Adenosylmethionine force field improved by dynamic Hirshfeld-I atomic charges for biomolecular simulation","volume":"29","author":"Saez","year":"2015","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e08186","DOI":"10.1016\/j.heliyon.2021.e08186","article-title":"Structural, vibrational, electronic properties, hirshfeld surface analysis topological and molecular docking studies of N-[2-(diethylamino) ethyl]-2-methoxy-5-methylsulfonylbenzamide","volume":"7","author":"Janani","year":"2021","journal-title":"Heliyon"},{"key":"ref_91","unstructured":"(2021, September 20). Uncharacterized Protein Rv1417, Accession Code P9WLY1. Available online: https:\/\/www.uniprot.org\/uniprot\/P9WLY1."},{"key":"ref_92","unstructured":"(2021, September 20). Probable Transmembrane Protein, Accession code I6XER9. Available online: https:\/\/www.uniprot.org\/uniprot\/I6XER9."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1021\/acs.jctc.1c01177","article-title":"Accelerated Ligand-Mapping Molecular Dynamics Simulations for the Detection of Recalcitrant Cryptic Pockets and Occluded Binding Sites","volume":"18","author":"Tan","year":"2022","journal-title":"J. Chem. Theory Comput."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3924","DOI":"10.1016\/j.csbj.2022.07.024","article-title":"Molecular dynamics analysis of the structural properties of the transglutaminases of Kutzneria albida and Streptomyces mobaraensis","volume":"20","author":"Giordano","year":"2022","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4736","DOI":"10.1021\/acs.jcim.2c00788","article-title":"Intermolecular Interactions in G Protein-Coupled Receptor Allosteric Sites at the Membrane Interface from Molecular Dynamics Simulations and Quantum Chemical Calculations","volume":"62","author":"Ding","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"160a","DOI":"10.1016\/j.bpj.2019.11.991","article-title":"Identifying and Exploiting Cryptic Pockets","volume":"118","author":"Bowman","year":"2020","journal-title":"Biophys. J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1529\/biophysj.104.041368","article-title":"Lessons of slicing membranes: Interplay of packing, free area, and lateral diffusion in phospholipid\/cholesterol bilayers","volume":"87","author":"Falck","year":"2004","journal-title":"Biophys. J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3951","DOI":"10.1529\/biophysj.105.076596","article-title":"Molecular simulation study of structural and dynamic properties of mixed DPPC\/DPPE bilayers","volume":"90","author":"Leekumjorn","year":"2006","journal-title":"Biophys. J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s00894-019-3964-0","article-title":"Physical properties of model biological lipid bilayers: Insights from all-atom molecular dynamics simulations","volume":"25","author":"Shahane","year":"2019","journal-title":"J. Mol. Model."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1248\/cpb.51.734","article-title":"Measurement of diffusion coefficients of parabens and steroids in water and 1-octanol","volume":"51","author":"Seki","year":"2003","journal-title":"Chem. Pharm. Bull."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jconrel.2017.12.027","article-title":"Do drug release studies from SEDDS make any sense?","volume":"271","author":"Jalil","year":"2018","journal-title":"J. Control. 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