{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T02:37:51Z","timestamp":1784860671236,"version":"3.55.0"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Psoriasis is chronic immune-mediated inflammatory disorder characterized by various comorbidities, erythematous plaques with silvery scale which can lead to psoriatic arthritis. The phosphodiesterase 4 (PDE4) protein is a potential drug target to control Psoriasis. In the current study, pharmacophore-based virtual screening of Diversity library of ChemDiv database was first performed, and then the screened hits were docked to the active site of PDE4 to choose the best binding modes. Forty-six hits generated during the virtual screening were prepared and docked to the PDE4 receptor by SP docking module of glide. The binding affinities of the selected hits were calculated by molecular docking and based on the affinities, ten hits were selected for the bioactivity scores prediction and ADMET analysis. Based on the ADMET profiling, four hits <jats:bold>D356-2630, C700-2058, G842-0420<\/jats:bold> and <jats:bold>F403-0203<\/jats:bold> were processed to MD simulations for stability analysis. The outcomes showed that these compounds showed strong binding with proteins with better binding free energies. Based on the results of our study, we proposed that these hits can function as lead in the biological assays and in vitro studies are required to develop the novel drug candidates.<\/jats:p>","DOI":"10.1371\/journal.pone.0305934","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T18:26:09Z","timestamp":1731522369000},"page":"e0305934","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Insilico discovery of novel Phosphodiesterase 4 (PDE4) inhibitors for the treatment of psoriasis: Insights from computer aided drug design approaches"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2565-6573","authenticated-orcid":true,"given":"Abdullah R.","family":"Alanzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed S.","family":"Alsalhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramzi A.","family":"Mothana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawaher H.","family":"Alqahtani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moneerah J.","family":"Alqahtani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"pone.0305934.ref001","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-immunol-032713-120225","article-title":"Immunology of psoriasis","volume":"32","author":"MA Lowes","year":"2014","journal-title":"Annual review of immunology"},{"issue":"3","key":"pone.0305934.ref002","doi-asserted-by":"crossref","first-page":"170","DOI":"10.7861\/clinmed.2021-0257","article-title":"Psoriasis: a brief overview","volume":"21","author":"A Raharja","year":"2021","journal-title":"Clinical Medicine"},{"issue":"1","key":"pone.0305934.ref003","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3390\/pharmaceutics16010023","article-title":"Phosphodiesterase-4 Inhibition in the Management of Psoriasis","volume":"16","author":"EL Crowley","year":"2023","journal-title":"Pharmaceutics"},{"key":"pone.0305934.ref004","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2147\/PTT.S303634","article-title":"Phosphodiesterase-4 inhibition in psoriasis","author":"M Milakovic","year":"2021","journal-title":"Psoriasis: Targets and Therapy"},{"key":"pone.0305934.ref005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13555-013-0023-0","article-title":"Phosphodiesterase 4 inhibition in the treatment of psoriasis, psoriatic arthritis and other chronic inflammatory diseases","volume":"3","author":"M Wittmann","year":"2013","journal-title":"Dermatology and therapy"},{"issue":"19","key":"pone.0305934.ref006","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1001\/jama.2020.4006","article-title":"Pathophysiology, clinical presentation, and treatment of psoriasis: a review","volume":"323","author":"AW Armstrong","year":"2020","journal-title":"Jama"},{"issue":"6","key":"pone.0305934.ref007","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.3390\/ijms20061475","article-title":"Psoriasis pathogenesis and treatment","volume":"20","author":"A Rendon","year":"2019","journal-title":"International journal of molecular sciences"},{"issue":"1","key":"pone.0305934.ref008","doi-asserted-by":"crossref","first-page":"e14669","DOI":"10.1111\/dth.14669","article-title":"Phosphodiesterase inhibitors and prostaglandin analogues in dermatology: A comprehensive review","volume":"34","author":"N Yazdanian","year":"2021","journal-title":"Dermatologic Therapy"},{"issue":"3","key":"pone.0305934.ref009","doi-asserted-by":"crossref","first-page":"69","DOI":"10.2340\/00015555-3386","article-title":"Psoriasis and treatment: past, present and future aspects","volume":"100","author":"C Reid","year":"2020","journal-title":"Acta dermato-venereologica"},{"issue":"3","key":"pone.0305934.ref010","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1016\/j.jaad.2017.11.056","article-title":"Phosphodiesterase 4 inhibitors","volume":"78","author":"R Zebda","year":"2018","journal-title":"Journal of the American Academy of Dermatology"},{"key":"pone.0305934.ref011","first-page":"409585","article-title":"Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases","volume":"9","author":"H Li","year":"2018","journal-title":"Frontiers in pharmacology"},{"issue":"1","key":"pone.0305934.ref012","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s13311-014-0309-7","article-title":"Phosphodiesterase-4 (PDE4) molecular pharmacology and Alzheimer\u2019s disease","volume":"12","author":"ME Gurney","year":"2015","journal-title":"Neurotherapeutics"},{"key":"pone.0305934.ref013","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1007\/s40265-015-0439-1","article-title":"Apremilast: a review in psoriasis and psoriatic arthritis","volume":"75","author":"ED Deeks","year":"2015","journal-title":"Drugs"},{"issue":"5","key":"pone.0305934.ref014","first-page":"1","article-title":"Apremilast in the treatment of psoriasis and psoriatic arthritis","volume":"20","author":"M Gooderham","year":"2015","journal-title":"Skin Therapy Lett"},{"issue":"3","key":"pone.0305934.ref015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13205-023-03912-5","article-title":"Discovery of novel anticancer flavonoids as potential HDAC2 inhibitors: virtual screening approach based on molecular docking, DFT and molecular dynamics simulations studies","volume":"14","author":"A Shah","year":"2024","journal-title":"3 Biotech"},{"key":"pone.0305934.ref016","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.gene.2017.09.034","article-title":"Design, virtual screening, molecular docking and molecular dynamics studies of novel urushiol derivatives as potential HDAC2 selective inhibitors","volume":"637","author":"H Zhou","year":"2017","journal-title":"Gene"},{"issue":"28","key":"pone.0305934.ref017","doi-asserted-by":"crossref","first-page":"e202202069","DOI":"10.1002\/slct.202202069","article-title":"In\u2010silico Computational Investigations of AntiViral Lignan Derivatives as Potent Inhibitors of SARS CoV\u20102","volume":"7","author":"DK Sureja","year":"2022","journal-title":"ChemistrySelect"},{"key":"pone.0305934.ref018","first-page":"647","article-title":"PHASE: a new engine for pharmacophore perception, 3D QSAR model development, and 3D database screening: 1. Methodology and preliminary results","volume":"20","author":"SL Dixon","year":"2006","journal-title":"JJoc-amd"},{"key":"pone.0305934.ref019","first-page":"681","article-title":"Epik: a software program for pK a prediction and protonation state generation for drug-like molecules","volume":"21","author":"JC Shelley","year":"2007","journal-title":"JJoc-amd"},{"issue":"3","key":"pone.0305934.ref020","first-page":"221","article-title":"Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"G Madhavi Sastry","year":"2013","journal-title":"JJoc-amd"},{"key":"pone.0305934.ref021","first-page":"19","volume":"174","author":"NB Sadeer","year":"2019","journal-title":"Chemical profiling, antioxidant, enzyme inhibitory and molecular modelling studies on the leaves and stem bark extracts of three African medicinal plants"},{"issue":"8","key":"pone.0305934.ref022","first-page":"2553","article-title":"Improving the prediction of absolute solvation free energies using the next generation OPLS force field","volume":"8","author":"D Shivakumar","year":"2012","journal-title":"JJoct, computation"},{"issue":"2","key":"pone.0305934.ref023","first-page":"203","article-title":"Discovery of fungal denitrification inhibitors by targeting copper nitrite reductase from Fusarium oxysporum","volume":"57","author":"M Matsuoka","year":"2017","journal-title":"JJoCI"},{"key":"pone.0305934.ref024","first-page":"91","volume":"10","author":"T Khan","year":"2017","journal-title":"Molecular docking, PASS analysis, bioactivity score prediction, synthesis, characterization and biological activity evaluation of a functionalized 2-butanone thiosemicarbazone ligand and its complexes"},{"issue":"5","key":"pone.0305934.ref025","first-page":"1663","volume":"21","author":"FE Agamah","year":"2020","journal-title":"Computational\/in silico methods in drug target and lead prediction"},{"key":"pone.0305934.ref026","first-page":"1177932219865533","article-title":"Homology modelling and molecular docking studies of selected substituted benzo [d] imidazol-1-yl) methyl) benzimidamide scaffolds on Plasmodium falciparum adenylosuccinate lyase receptor","volume":"13","author":"GO Oduselu","year":"2019","journal-title":"JB, insights b"},{"issue":"1","key":"pone.0305934.ref027","first-page":"1","article-title":"In silico design and pharmacokinetics investigation of some novel hepatitis C virus NS5B inhibitors: pharmacoinformatics approach","volume":"46","author":"S Ejeh","year":"2022","journal-title":"JBotNRC"},{"key":"pone.0305934.ref028","doi-asserted-by":"crossref","unstructured":"Bowers KJ, Chow E, Xu H, Dror RO, Eastwood MP, Gregersen BA, et al., editors. Scalable algorithms for molecular dynamics simulations on commodity clusters. Proceedings of the 2006 ACM\/IEEE Conference on Supercomputing; 2006.","DOI":"10.1109\/SC.2006.54"},{"issue":"20","key":"pone.0305934.ref029","first-page":"10096","article-title":"A modified TIP3P water potential for simulation with Ewald summation","volume":"121","author":"DJ Price","year":"2004","journal-title":"JTJocp"},{"key":"pone.0305934.ref030","unstructured":"Prema V, Meena A, Ramalakshmi NJCc-add. In-silico Design, ADMET Screening, Prime MM-GBSA Binding Free Energy Calculation and MD Simulation of Some Novel Phenothiazines as 5HT6R Antagonists Targeting Alzheimer\u2019s Disease."},{"issue":"4","key":"pone.0305934.ref031","first-page":"1518","article-title":"How molecular size impacts RMSD applications in molecular dynamics simulations","volume":"13","author":"K Sargsyan","year":"2017","journal-title":"JJoct, computation"},{"issue":"3","key":"pone.0305934.ref032","first-page":"e0119264","article-title":"Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis","volume":"10","author":"L Mart\u00ednez","year":"2015","journal-title":"JPo"},{"issue":"9","key":"pone.0305934.ref033","first-page":"1276","volume":"11","author":"SS Khan","year":"2021","journal-title":"Design and Prototyping of Genetically Encoded Arsenic Biosensors Based on Transcriptional Regulator AfArsR"},{"issue":"20","key":"pone.0305934.ref034","first-page":"7731","article-title":"Comparison of MM\/GBSA calculations based on explicit and implicit solvent simulations","volume":"15","author":"F Godschalk","year":"2013","journal-title":"JPCCP"},{"issue":"23","key":"pone.0305934.ref035","first-page":"12788","article-title":"Thermodynamics and kinetics of drug-target binding by molecular simulation","volume":"120","author":"S Decherchi","year":"2020","journal-title":"JCR"},{"issue":"6","key":"pone.0305934.ref036","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1111\/bjd.14164","article-title":"Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate\u2010to\u2010severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2)","volume":"173","author":"C Paul","year":"2015","journal-title":"British Journal of Dermatology"},{"issue":"8","key":"pone.0305934.ref037","doi-asserted-by":"crossref","first-page":"734","DOI":"10.36849\/JDD.2020.5370","article-title":"Roflumilast cream improves signs and symptoms of plaque psoriasis: results from a phase 1\/2a randomized, controlled study. Journal of Drugs in Dermatology","volume":"19","author":"KA Papp","year":"2020","journal-title":"JDD"},{"issue":"2","key":"pone.0305934.ref038","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.jaad.2019.06.1288","article-title":"Crisaborole 2% ointment for the treatment of intertriginous, anogenital, and facial psoriasis: a double-blind, randomized, vehicle-controlled trial","volume":"82","author":"PW Hashim","year":"2020","journal-title":"Journal of the American Academy of Dermatology"},{"key":"pone.0305934.ref039","unstructured":"Padda IS, Tripp J. Phosphodiesterase inhibitors. 2020."},{"issue":"3","key":"pone.0305934.ref040","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1080\/13543776.2022.2026328","article-title":"Phosphodiesterase\u20114 inhibitors: a review of current developments (2013\u20132021)","volume":"32","author":"Z Liu","year":"2022","journal-title":"Expert Opinion on Therapeutic Patents"},{"key":"pone.0305934.ref041","doi-asserted-by":"crossref","first-page":"104851","DOI":"10.1016\/j.compbiomed.2021.104851","article-title":"In silico methods and tools for drug discovery","volume":"137","author":"B Shaker","year":"2021","journal-title":"Computers in biology and medicine"},{"issue":"3","key":"pone.0305934.ref042","first-page":"186","article-title":"In silico methods for drug repurposing and pharmacology","volume":"8","author":"RA Hodos","year":"2016","journal-title":"Wiley Interdisciplinary Reviews: Systems Biology and Medicine"},{"issue":"9","key":"pone.0305934.ref043","doi-asserted-by":"crossref","first-page":"731","DOI":"10.2174\/1570178615666180430120235","article-title":"In-Silico Analysis and Molecular Docking Studies of Potential Phosphodiesterase 4 Inhibitors using Ventilago Isolates","volume":"15","author":"A Manakadan","year":"2018","journal-title":"Letters in Organic Chemistry"},{"key":"pone.0305934.ref044","doi-asserted-by":"crossref","unstructured":"Sunitha Sukumaran MM, Sneha S, Arjun B, Sathianarayanan S, Saranya T. Insilico analysis of acridone against TNF-\u03b1 and PDE4 targets for the treatment of psoriasis. 2020.","DOI":"10.26452\/ijrps.v11iSPL4.4286"},{"issue":"2","key":"pone.0305934.ref045","doi-asserted-by":"crossref","first-page":"187","DOI":"10.2174\/157340607780059521","article-title":"Pharmacophore modeling in drug discovery and development: an overview","volume":"3","author":"SA Khedkar","year":"2007","journal-title":"Medicinal Chemistry"},{"issue":"3","key":"pone.0305934.ref046","first-page":"749","article-title":"Pharmacophore modeling in drug discovery: methodology and current status. Journal of the Turkish Chemical Society Section A","volume":"8","author":"MT Muhammed","year":"2021","journal-title":"Chemistry"},{"issue":"11","key":"pone.0305934.ref047","first-page":"e0273256","volume":"17","author":"S MA Kawsar","year":"2022","journal-title":"Potential SARS-CoV-2 RdRp inhibitors of cytidine derivatives: Molecular docking, molecular dynamic simulations, ADMET, and POM analyses for the identification of pharmacophore sites"},{"issue":"2","key":"pone.0305934.ref048","first-page":"1","article-title":"Virtual screening in drug discovery","volume":"20","author":"AR Patel","year":"2021","journal-title":"Journal Of Veterinary Pharmacology And Toxicology"},{"key":"pone.0305934.ref049","first-page":"4109","volume-title":"New trends in virtual screening","author":"WP Walters","year":"2020"},{"key":"pone.0305934.ref050","first-page":"105850","volume":"125","author":"MA Hosen","year":"2022","journal-title":"Synthesis, antimicrobial, molecular docking and molecular dynamics studies of lauroyl thymidine analogs against SARS-CoV-2: POM study and identification of the pharmacophore sites"},{"issue":"22","key":"pone.0305934.ref051","first-page":"7016","volume":"26","author":"MR Amin","year":"2021","journal-title":"Synthesis, antimicrobial, anticancer, PASS, molecular docking, molecular dynamic simulations & pharmacokinetic predictions of some methyl \u03b2-D-galactopyranoside analogs"},{"issue":"3","key":"pone.0305934.ref052","first-page":"159","article-title":"Thermochemical, PASS, molecular docking, drug-likeness and in silico ADMET prediction of cytidine derivatives against HIV-1 reverse transcriptase","volume":"72","author":"SMA Kawsar","year":"2021","journal-title":"JRdC"},{"issue":"1","key":"pone.0305934.ref053","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1021\/acs.molpharmaceut.0c01013","article-title":"Bioactivity comparison across multiple machine learning algorithms using over 5000 datasets for drug discovery","volume":"18","author":"TR Lane","year":"2020","journal-title":"Molecular pharmaceutics"},{"issue":"4","key":"pone.0305934.ref054","doi-asserted-by":"crossref","first-page":"e1010029","DOI":"10.1371\/journal.pcbi.1010029","article-title":"Bioactivity assessment of natural compounds using machine learning models trained on target similarity between drugs","volume":"18","author":"V Periwal","year":"2022","journal-title":"PLoS computational biology"},{"issue":"2","key":"pone.0305934.ref055","first-page":"59","article-title":"An optimization and pharmacokinetic studies of some thymidine derivatives","volume":"4","author":"SM Kawsar","year":"2020","journal-title":"JTC, Chemistry T"},{"issue":"5","key":"pone.0305934.ref056","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.drudis.2019.03.015","article-title":"ADMET modeling approaches in drug discovery","volume":"24","author":"LL Ferreira","year":"2019","journal-title":"Drug discovery today"},{"issue":"7","key":"pone.0305934.ref057","first-page":"181","article-title":"Drug discovery and ADMET process: a review","volume":"3","author":"PS Patil","year":"2016","journal-title":"Int J Adv Res Biol Sci"},{"key":"pone.0305934.ref058","first-page":"1385","article-title":"Identification of bioactive phytoconstituents from the plant Euphorbia hirta as potential inhibitor of SARS-CoV-2: an in-silico approach","volume":"12","author":"G Parmar","year":"2022","journal-title":"JBRAC"},{"issue":"2","key":"pone.0305934.ref059","first-page":"60","article-title":"In silico drug discovery of novel small lead compounds targeting nipah virus attachment glycoprotein","volume":"6","author":"AP Shah","year":"2018","journal-title":"JJoIHS"},{"issue":"1","key":"pone.0305934.ref060","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3390\/pr9010071","article-title":"Molecular dynamics simulations in drug discovery and pharmaceutical development","volume":"9","author":"OM Salo-Ahen","year":"2020","journal-title":"Processes"},{"key":"pone.0305934.ref061","doi-asserted-by":"crossref","first-page":"100880","DOI":"10.1016\/j.imu.2022.100880","article-title":"Molecular modeling in drug discovery","volume":"29","author":"TI Adelusi","year":"2022","journal-title":"Informatics in Medicine Unlocked"},{"key":"pone.0305934.ref062","first-page":"1","author":"MR Amin","year":"2021","journal-title":"Methyl \u03b2-D-galactopyranoside esters as potential inhibitors for SARS-CoV-2 protease enzyme: synthesis, antimicrobial, PASS, molecular docking, molecular dynamics simulations and quantum computations"},{"issue":"6","key":"pone.0305934.ref063","first-page":"1107","volume":"59","author":"NS Munia","year":"2023","journal-title":"Uridine Derivatives: Synthesis, Biological Evaluation, and In Silico Studies as Antimicrobial and Anticancer Agents"},{"key":"pone.0305934.ref064","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/B978-0-323-90608-1.00006-X","volume-title":"Computer aided drug design (CADD): From ligand-based methods to structure-based approaches","author":"A Shah","year":"2022"},{"issue":"9","key":"pone.0305934.ref065","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/j.drudis.2020.07.005","article-title":"Advancing computer-aided drug discovery (CADD) by big data and data-driven machine learning modeling","volume":"25","author":"L Zhao","year":"2020","journal-title":"Drug discovery today"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0305934","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T18:26:26Z","timestamp":1731522386000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0305934"}},"subtitle":[],"editor":[{"given":"Sheikh Arslan","family":"Sehgal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,13]]},"references-count":65,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0305934","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,13]]}}}