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This CRTH2\u2010PGD2 signaling pathway has become a target for treating allergic and type 2 inflammation dependent diseases, with many inhibitors developed to target the PGD2 binding pocket. One of such inhibitors is the ramatroban analog, CT\u2010133, which exhibited therapeutic potency cigarette smoke\u2010induced acute lung injury in patients. Nonetheless, the molecular mechanism and structural dynamics that accounts for its therapeutic prowess remain unclear. Employing computational tools, this study revealed that although the carboxylate moiety in CT\u2010133 and the native agonist PGD2 aided in their stability within the CRTH2 binding pocket, the tetrahydrocarbazole group of CT\u2010133 engaged in strong interactions with binding pocket residues which could have formed as the basis of the antagonistic advantage of CT\u2010133. Tetrahydrocarbazole group interactions also enhanced the relative stability CT\u2010133 within the binding pocket which consequently favored CT\u2010133 binding affinity. CT\u2010133 binding also induced an inactive or \u2018desensitized\u2019 state in the helix 8 of CRTH2 which could conversely favor the recruitment of arrestin. These revelations would aid in the speedy development of small molecule inhibitors of CRTH2 in the treatment of type 2 inflammation dependent diseases.<\/jats:p>","DOI":"10.1002\/cbdv.201900548","type":"journal-article","created":{"date-parts":[[2020,2,8]],"date-time":"2020-02-08T02:54:45Z","timestamp":1581130485000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lipid\u2010Embedded Molecular Dynamics Simulation Model for Exploring the Reverse Prostaglandin D2 Agonism of CT\u2010133 towards CRTH2 in the Treatment of Type\u20102 Inflammation Dependent Diseases"],"prefix":"10.1002","volume":"17","author":[{"given":"Abdul Rashid","family":"Issahaku","sequence":"first","affiliation":[{"name":"Molecular Bio-computation and Drug Design Laboratory School of Health Sciences University of KwaZulu-Natal, Westville Campus  Durban 4001 South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clement","family":"Agoni","sequence":"additional","affiliation":[{"name":"Molecular Bio-computation and Drug Design Laboratory School of Health Sciences University of KwaZulu-Natal, Westville Campus  Durban 4001 South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ransford O.","family":"Kumi","sequence":"additional","affiliation":[{"name":"Molecular Bio-computation and Drug Design Laboratory School of Health Sciences University of KwaZulu-Natal, Westville Campus  Durban 4001 South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fisayo A.","family":"Olotu","sequence":"additional","affiliation":[{"name":"Molecular Bio-computation and Drug Design Laboratory School of Health Sciences University of KwaZulu-Natal, Westville Campus  Durban 4001 South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8711-7783","authenticated-orcid":false,"given":"Mahmoud E. 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