{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:36:33Z","timestamp":1784306193783,"version":"3.55.0"},"reference-count":77,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T00:00:00Z","timestamp":1635292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Deanship at King Khalid University and the Ministry of Education in KSA for funding this research work through the project number","award":["IFP-KKU-2020\/14."],"award-info":[{"award-number":["IFP-KKU-2020\/14."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The use of pharmaceuticals to treat Major Depressive Disorder (MDD) has several drawbacks, including severe side effects. Natural compounds with great efficacy and few side effects are in high demand due to the global rise in MDD and ineffective treatment. Yohimbine, a natural compound, has been used to treat various ailments, including neurological conditions, since ancient times. Serotonergic neurotransmission plays a crucial role in the pathogenesis of depression; thus, serotonergic receptor agonist\/antagonistic drugs are promising anti-depressants. Yohimbine was investigated in this study to determine its antidepressant activity using molecular docking and pharmacokinetic analyses. Additionally, the in silico mutational study was carried out to understand the increase in therapeutic efficiency using site-directed mutagenesis. Conformational changes and fluctuations occurring during wild type and mutant serotonergic receptor, 5-hydroxytryptamine receptors 1A (5HT1A) and yohimbine were assessed by molecular dynamics MD simulation studies. Yohimbine was found to satisfy all the parameters for drug-likeness and pharmacokinetics analysis. It was found to possess a good dock score and hydrogen-bond interactions with wild type 5HT1A structure. Our findings elaborate the substantial efficacy of yohimbine against MDD; however, further bench work studies may be carried out to prove the same.<\/jats:p>","DOI":"10.3390\/cimb43030127","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T23:26:38Z","timestamp":1635377198000},"page":"1805-1827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Investigation of Antidepressant Properties of Yohimbine by Employing Structure-Based Computational Assessments"],"prefix":"10.3390","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4811-2154","authenticated-orcid":false,"given":"Munazzah","family":"Tasleem","sequence":"first","affiliation":[{"name":"School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu 610054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulwahed","family":"Alrehaily","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Islamic University of Madinah, P.O. Box 170, Madinah 42351, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahani M.","family":"Almeleebia","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, P.O. Box 61413, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7096-0221","authenticated-orcid":false,"given":"Mohammad Y.","family":"Alshahrani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, P.O. Box 61413, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9500-4623","authenticated-orcid":false,"given":"Irfan","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, P.O. Box 61413, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8677-9240","authenticated-orcid":false,"given":"Mohammed","family":"Asiri","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, P.O. Box 61413, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadiyah M.","family":"Alabdallah","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3443-386X","authenticated-orcid":false,"given":"Mohd","family":"Saeed","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Sciences University of Hail, P.O. Box 2440, Hail 2440, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: A systematic analysis for the global burden of disease study 2017","volume":"392","author":"James","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/B978-0-12-388408-4.00005-8","article-title":"Ontologies for human behavior analysis and their application to clinical data","volume":"103","author":"Hastings","year":"2012","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_3","unstructured":"Bains, N., Abdijadid, S., and Miller, J.L. (2021). Major Depressive Disorder (Nursing), StatPearls."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S2215-0366(19)30475-4","article-title":"The burden of mental disorders across the states of India: The global burden of disease study 1990\u20132017","volume":"7","author":"Sagar","year":"2020","journal-title":"Lancet Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/515180a","article-title":"Mental health: A world of depression","volume":"515","author":"Smith","year":"2014","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"220","DOI":"10.4103\/0019-5545.117131","article-title":"Diagnostic and statistical manual of mental disorders 5: A quick glance","volume":"55","author":"Vahia","year":"2013","journal-title":"Indian J. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/S0140-6736(16)31678-6","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990\u20132015: A systematic analysis for the Global Burden of Disease Study 2015","volume":"388","author":"Vos","year":"2016","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.neuropharm.2011.02.017","article-title":"Modeling treatment-resistant depression","volume":"61","author":"Samuels","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13041-017-0306-y","article-title":"The role of 5-HT receptors in depression","volume":"10","author":"Yohn","year":"2017","journal-title":"Mol. Brain."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/sj.mp.4001949","article-title":"Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: A meta-analysis of monoamine depletion studies","volume":"12","author":"Ruhe","year":"2007","journal-title":"Mol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2147\/JEP.S133778","article-title":"Diuretic activity of the aqueous crude extract and hot tea infusion of Moringa stenopetala (Baker f.) Cufod. leaves in rats","volume":"9","author":"Fekadu","year":"2017","journal-title":"J. Exp. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"191","DOI":"10.31887\/DCNS.2006.8.2\/fduval","article-title":"Treatments in depression","volume":"8","author":"Duval","year":"2006","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_13","first-page":"CD004853","article-title":"Psychotherapeutic treatments for older depressed people","volume":"1","author":"Wilson","year":"2008","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1002\/gps.1620","article-title":"Psychological treatment of late-life depression: A meta-analysis of randomized controlled trials","volume":"21","author":"Cuijpers","year":"2006","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_15","first-page":"30","article-title":"The use of electroconvulsive therapy in atypical psychotic presentations: A case review","volume":"4","author":"Montgomery","year":"2007","journal-title":"Psychiatry"},{"key":"ref_16","first-page":"2345","article-title":"The NeuroStar TMS device: Conducting the FDA approved protocol for treatment of depression","volume":"45","author":"Horvath","year":"2010","journal-title":"J. Vis. Exp."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"60","DOI":"10.5298\/1081-5937-39.2.03","article-title":"Yoga as therapy in psychiatric disorders: Past, present, and future","volume":"39","author":"Gangadhar","year":"2011","journal-title":"Biofeedback"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S34","DOI":"10.1016\/S0165-0327(14)70007-2","article-title":"Managing the side effects associated with commonly used treatments for bipolar depression","volume":"169","author":"Kemp","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"79","DOI":"10.4088\/PCC.v06n0206","article-title":"Suicidality as a possible side effect of antidepressant treatment","volume":"6","author":"Culpepper","year":"2004","journal-title":"Prim. Care Companion J. Clin. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1176\/appi.ps.51.9.1130","article-title":"A review of herbal medicines for psychiatric disorders","volume":"51","author":"Beaubrun","year":"2000","journal-title":"Psychiatr. Serv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1001\/archpsyc.55.11.1033","article-title":"Herbal remedies in psychiatric practice","volume":"55","author":"Wong","year":"1998","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S70","DOI":"10.1038\/sj.ijir.3900508","article-title":"Yohimbine in erectile dysfunction: The facts","volume":"12","author":"Morales","year":"2000","journal-title":"Int. J. Impot. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1006\/phrs.2001.0870","article-title":"The potential antidiabetic activity of some alpha-2 adrenoceptor antagonists","volume":"44","author":"Ahmed","year":"2001","journal-title":"Pharmacol. Res."},{"key":"ref_24","first-page":"S17","article-title":"Pharmacologic treatment of erectile dysfunction","volume":"4","author":"Steers","year":"2002","journal-title":"Rev. Urol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3109\/10253890.2012.708951","article-title":"Effects of noradrenergic stimulation on memory in patients with major depressive disorder","volume":"16","author":"Wingenfeld","year":"2013","journal-title":"Stress"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1586\/eri.09.42","article-title":"Microbial toxins: Current research and future trends","volume":"7","author":"Mohamadzadeh","year":"2009","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1192\/bjp.154.3.321","article-title":"Bipolar affective disorder: Causes and prevention of relapse","volume":"154","author":"Silverstone","year":"1989","journal-title":"Br. J. Psychiatry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1176\/ajp.156.11.1787","article-title":"Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder","volume":"156","author":"Bremner","year":"1999","journal-title":"Am. J. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1212\/WNL.37.2.215","article-title":"Oral yohimbine in human autonomic failure","volume":"37","author":"Onrot","year":"1987","journal-title":"Neurology"},{"key":"ref_30","unstructured":"(2021, July 08). Drug Bank Yohimbine. Updated on 8 July 2018. Available online: https:\/\/www.drugbank.ca\/drugs\/DB01392."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1016\/S1734-1140(13)71510-X","article-title":"Potential role of G protein-coupled receptor (GPCR) heterodimerization in neuropsychiatric disorders: A focus on depression","volume":"65","author":"Szafran","year":"2013","journal-title":"Pharmacol. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1126\/science.1249489","article-title":"Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator","volume":"344","author":"Wu","year":"2014","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.neuropharm.2009.12.004","article-title":"From synapse to nucleus: Novel targets for treating depression","volume":"58","author":"Covington","year":"2010","journal-title":"Neuropharmacology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with Alpha Fold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/(SICI)1098-2396(200002)35:2<79::AID-SYN1>3.0.CO;2-X","article-title":"Agonist and antagonist actions of yohimbine as compared to fluparoxan at \u00b12-adrenergic receptors (AR)s, serotonin (5-HT)1A, 5-HT1B, 5-HT1D and dopamine D2 and D3 receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states","volume":"35","author":"Millan","year":"2000","journal-title":"Synapse"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s40263-013-0071-0","article-title":"Serotonin 5-HT1A receptors as targets for agents to treat psychiatric disorders: Rationale and current status of research","volume":"27","author":"Celada","year":"2013","journal-title":"CNS Drugs"},{"key":"ref_37","first-page":"252","article-title":"The therapeutic role of 5-HT1A and 5-HT2A receptors in depression","volume":"29","author":"Celada","year":"2004","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_38","unstructured":"(2021, August 30). PubChem Compound Summary for CID 8969, Yohimbine. National Center for Biotechnology Information, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Katya Tsaioun, S.A.K. (2011). In silico adme\/tox Predictions. ADMET for Medicinal Chemists: A Practical Guide, John Wiley & Sons.","DOI":"10.1002\/9780470915110"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3867","DOI":"10.1021\/jm000292e","article-title":"Prediction of drug absorption using multivariate statistics","volume":"43","author":"Egan","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13321-018-0283-x","article-title":"ADMETlab: A platform for systematic ADMET evaluation based on a comprehensively collected ADMET database","volume":"10","author":"Dong","year":"2018","journal-title":"J. Cheminform."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Shukla, A., Sharma, P., Prakash, O., Singh, M., Kalani, K., Khan, F., Bawankule, D.U., Luqman, S., and Srivastava, S.K. (2014). QSAR and docking studies on capsazepine derivatives for immunomodulatory and anti-inflammatory activity. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100797"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S0723-2020(87)80008-5","article-title":"Production of mycotoxins by Penicillium Species","volume":"10","author":"Pitt","year":"1987","journal-title":"Syst. Appl. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3784","DOI":"10.1093\/nar\/gkg563","article-title":"ExPASy: The proteomics server for in-depth protein knowledge and analysis","volume":"31","author":"Gasteiger","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"D225","DOI":"10.1093\/nar\/gkq1189","article-title":"CDD: A Conserved Domain Database for the functional annotation of proteins","volume":"39","author":"Lu","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"D493","DOI":"10.1093\/nar\/gkx922","article-title":"20 years of the SMART protein domain annotation resource","volume":"46","author":"Letunic","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D115","DOI":"10.1093\/nar\/gkh131","article-title":"UniProt: The universal protein knowledgebase","volume":"32","author":"Apweiler","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/nar\/30.1.38","article-title":"The Ensembl genome database project","volume":"30","author":"Hubbard","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"W141","DOI":"10.1093\/nar\/gkv461","article-title":"SIFTER search: A web server for accurate phylogeny-based protein function prediction","volume":"43","author":"Sahraeian","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"W362","DOI":"10.1093\/nar\/gkl124","article-title":"ScanProsite: Detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins","volume":"34","author":"Sigrist","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/1479-7364-4-3-207","article-title":"The CATH database","volume":"4","author":"Knudsen","year":"2010","journal-title":"Hum. Genom."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"D542","DOI":"10.1093\/nar\/gkx1104","article-title":"iPTMnet: An integrated resource for protein post-translational modification network discovery","volume":"46","author":"Huang","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.2174\/1570180811666140717190217","article-title":"Structural characterization, homology modeling and docking studies of ARG674 mutation in MyH8 gene associated with trismus-pseudocamptodactyly syndrome","volume":"11","author":"Tasleem","year":"2014","journal-title":"Lett. Drug Des. Discov."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/bioinformatics\/16.4.404","article-title":"The PSIPRED protein structure prediction server","volume":"16","author":"McGuffin","year":"2000","journal-title":"Bioinformatics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5.6.1","DOI":"10.1002\/cpbi.3","article-title":"Comparative protein structure modeling using MODELLER","volume":"54","author":"Webb","year":"2016","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1093\/nar\/gkg520","article-title":"SWISS-MODEL: An. automated protein homology-modeling server","volume":"31","author":"Schwede","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"D465","DOI":"10.1093\/nar\/gkq1091","article-title":"ModBase, a database of annotated comparative protein structure models, and associated resources","volume":"39","author":"Pieper","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 web portal for protein modeling, prediction and analysis","volume":"10","author":"Kelley","year":"2015","journal-title":"Nat. Protoc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1110\/ps.0236803","article-title":"Can correct protein models be identified?","volume":"12","author":"Wallner","year":"2003","journal-title":"Protein Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W407","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins","volume":"35","author":"Wiederstein","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1002\/pro.5560020916","article-title":"Verification of protein structures: Patterns of nonbonded atomic interactions","volume":"2","author":"Colovos","year":"1993","journal-title":"Protein Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/prot.10286","article-title":"Structure validation by Calpha geometry: Phi, psi and Cbeta deviation","volume":"50","author":"Lovell","year":"2003","journal-title":"Proteins"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: A program to check the stereochemical quality of protein structures","volume":"26","author":"Laskowski","year":"1993","journal-title":"J. Appl. Crystallogr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/prot.10465","article-title":"Improved protein-ligand docking using GOLD","volume":"52","author":"Verdonk","year":"2003","journal-title":"Proteins"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1021\/ct700301q","article-title":"GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation","volume":"4","author":"Hess","year":"2008","journal-title":"J. Chem. Theory Comput."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1002\/jcc.1078","article-title":"An improved GROMOS96 force field for aliphatic hydrocarbons in the condensed phase","volume":"22","author":"Schuler","year":"2001","journal-title":"J. Comput. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e5472","DOI":"10.7717\/peerj.5472","article-title":"Simulations of lipid bilayers using the CHARMM36 force field with the TIP3P-FB and TIP4P-FB water models","volume":"6","author":"Sajadi","year":"2018","journal-title":"PeerJ"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6269","DOI":"10.1021\/j100308a038","article-title":"The missing term in effective pair potentials","volume":"91","author":"Berendsen","year":"1987","journal-title":"J. Phys. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"014101","DOI":"10.1063\/1.2408420","article-title":"Canonical sampling through velocity rescaling","volume":"126","author":"Bussi","year":"2007","journal-title":"J. Chem. Phys."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic transitions in single crystals: A new molecular dynamics method","volume":"52","author":"Parrinello","year":"1981","journal-title":"J. Appl. Phys."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1080\/08927028808080941","article-title":"A leap-frog algorithm for stochastic dynamics","volume":"1","author":"Berendsen","year":"1988","journal-title":"Molec. Simul."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"19","DOI":"10.5599\/admet.1.3.9","article-title":"What ADME tests should be conducted for preclinical studies?","volume":"1","author":"Wan","year":"2013","journal-title":"Admet. Dmpk."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4155\/fmc-2019-0206","article-title":"ADMET profiling of geographically diverse phytochemical using chemoinformatic tools","volume":"12","author":"Fatima","year":"2020","journal-title":"Future Med. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/s41586-021-03376-8","article-title":"Structural insights into the lipid and ligand regulation of serotonin receptors","volume":"592","author":"Xu","year":"2021","journal-title":"Nature"},{"key":"ref_77","unstructured":"Meyers, R.A. (2003). Protein Structure. Encyclopedia of Physical Science and Technology, Academic Press, Ramtech, Inc.. [3rd ed.]."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/43\/3\/127\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:21:31Z","timestamp":1760167291000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/43\/3\/127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,27]]},"references-count":77,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["cimb43030127"],"URL":"https:\/\/doi.org\/10.3390\/cimb43030127","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,27]]}}}