fa بررسی توانایی اتصال کاندیدهای دارویی با آنزیم HO-1 جهت کاهش درد ناشی از اختلالات مفصل گیجگاهی فکی (TMD) با استفاده از داکینگ مولکولی دندانپزشکی Dentistry پژوهشي اصیل Original Research <span style="font-size:12pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span b="" lang="AR-SA" style="font-family:" zar="">مقدمه و هدف</span></b><span b="" lang="AR-SA" style="font-family:" zar="">: </span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">HO</span></span><span dir="LTR" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">-</span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">1</span></span> <span b="" lang="AR-SA" style="font-family:" zar="">یک آنزیم مهم در کنترل درد و التهاب ناشی از اختلالات مفصل گیجگاهی فکی است. این مطالعه با هدف شناسایی ترکیبات دارویی موثر بر </span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">HO-1</span></span><b> </b><span b="" lang="AR-SA" style="font-family:" zar="">با استفاده از مدلسازی دارویی داکینگ مولکولی انجام شد.</span><span lang="FA" style="font-family:"B Zar""></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span b="" lang="AR-SA" style="font-family:" zar="">مواد</span></b><b> </b><b><span b="" lang="AR-SA" style="font-family:" zar="">و</span></b><b> </b><b><span b="" lang="AR-SA" style="font-family:" zar="">روش &shy;ها</span></b><span b="" dir="LTR" style="font-family:" zar="">:</span> <span b="" lang="FA" style="font-family:" zar="">این مطالعه به صورت علوم پایه انجام شد. جامعه مورد مطالعه شامل داروهای موجود در پایگاه اطلاعات دارویی</span><span b="" lang="FA" style="font-family:" zar="">.</span><span b="" lang="FA" style="font-family:" zar=""> معیار ورود، داروهای با تاثیرگذاری بیشتر و معیارهای خروج: داروهای با بیشترین عوارض بود. </span><span b="" lang="AR-SA" style="font-family:" zar="">ابتدا ساختار آنزیم&shy; </span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">HO-1</span></span> <span b="" lang="AR-SA" style="font-family:" zar="">از دیتابیس &quot;پروتئین دیتا بانک&quot; استخراج، سپس با استفاده از نرم افزارها و سرورهای دیسکاوری استودیو، یاسارا انرژی مینیمایزیشن و کایمرا، ابتدا ساختار لیگاندهای اضافی حذف و سپس ساختار پروتئین بهینه سازی شد. براساس دراگ بانک داروهایی که می&shy;توانند بیشترین اثر گذاری را داشته باشند شناسایی شد، سپس ترکیبات دارویی استخراج و توسط نرم افزار کم بایو تری دی و آوگادروو بهینه سازی شد. داکینگ مولکولی توسط نرم افزار مولگرو ویرچوال داکر 2019 انجام شد.</span><span lang="FA" style="font-family:"B Zar""></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span b="" lang="AR-SA" style="font-family:" zar="">یافته‌ها</span></b><b><span b="" dir="LTR" style="font-family:" zar="">:</span></b><b> </b><span b="" lang="AR-SA" style="font-family:" zar="">از بین ترکیبات دارویی مورد استفاده برای انجام برهمکنش با </span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">HO-1</span></span><span b="" lang="FA" style="font-family:" zar="">، به ترتیب<b> </b></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">NADH </span></span><span lang="AR-SA" style="font-size:11.0pt"><span b="" style="font-family:" zar="">> </span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">&nbsp;alpha</span></span><span dir="LTR" new="" roman="" style="font-family:" times=""><span style="color:black">-</span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">Tocopherol</span></span> <span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">succinate</span></span><span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black">> </span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">Vitamin</span></span> <span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">E</span></span><span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black">> </span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">Tryptophan</span></span><span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black"> > </span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">Isopropyl</span></span> <span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">Alcohol</span></span> <span b="" lang="FA" style="font-family:" zar="">بیشترین برهمکنش را داشتند که سطح انرژی برهمکنش آن&shy;ها به ترتیب برابر بود با 9050/192- < -1080/142- < 146/133- < 7108/95- < 6045/43- همچنین تعداد پیوندهای هیدروژنی مربوط به آن&shy;ها با </span>HO-1<span b="" lang="FA" style="font-family:" zar=""> به ترتیب برابر با 10 پیوند هیدروژنی، 1 پیوند، 2 پیوند، 2 پیوند و 3 پیوند هیدروژنی بود.</span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif">&nbsp;<b><span b="" lang="AR-SA" style="font-family:" zar="">نتیجه &shy;گیری:</span></b> <span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black">ترکیب</span></span> <span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black">دارویی</span></span> <span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">NADH</span></span><span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black"> بالاترین</span></span> <span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black">برهمکنش را با آنزیم </span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">HO</span></span><span dir="LTR" lang="EN-GB" new="" roman="" style="font-family:" times=""><span style="color:black">-</span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">1</span></span> <span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black">داشت. ترکیبات دارویی</span></span> <span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">alpha</span></span><span dir="LTR" new="" roman="" style="font-family:" times=""><span style="color:black">-</span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">Tocopherol</span></span> <span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">succinate</span></span><span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black"> و </span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">Vitamin</span></span> <span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">E</span></span><span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black"> برهمکنش بالایی با آنزیم </span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">HO</span></span><span dir="LTR" lang="EN-GB" new="" roman="" style="font-family:" times=""><span style="color:black">-</span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">1</span></span> <span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black">داشتند. ترکیبات دارویی </span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">Tryptophan</span></span><span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black"> و </span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">Isopropyl</span></span><span dir="LTR" new="" roman="" style="font-family:" times=""><span style="color:black"> Alcohol</span></span><span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black"> برهمکنش مناسبی با آنزیم </span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">HO</span></span><span dir="LTR" lang="EN-GB" new="" roman="" style="font-family:" times=""><span style="color:black">-</span></span><span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">1</span></span> <span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black">داشتند</span></span><span b="" lang="FA" style="font-family:" zar="">. </span><span dir="LTR" new="" roman="" style="font-family:" times=""><span style="color:black">HO</span></span><span dir="LTR" lang="EN-GB" new="" roman="" style="font-family:" times=""><span style="color:black">-</span></span><span dir="LTR" new="" roman="" style="font-family:" times=""><span style="color:black">1</span></span> <span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black">یک آنزیم مناسب جهت کنترل درد و التهاب ناشی از</span></span> <span dir="LTR" lang="EN-GB" style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">TMD</span></span> <span b="" lang="AR-SA" style="font-family:" zar=""><span style="color:black">است</span></span><span b="" lang="FA" style="font-family:" zar="">.</span></span></span></span></span></span><br> &nbsp; <span style="font-size:12pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">Background and Aim:</span></span></b><span style="font-size:11.0pt"><span new="" roman="" style="font-family:" times=""> HO-1 is an important enzyme in controlling pain and inflammation caused by temporomandibular joint disorders. This study aimed to identify pharmaceutical compounds effective on HO-1 using molecular docking drug modeling.</span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">Materials and Methods:</span></span></b><span style="font-size:11.0pt"><span new="" roman="" style="font-family:" times=""> This study was conducted as a basic science. The study population included drugs available in the drug information database. The inclusion criterion involved initial screening to identify drugs with greater efficacy, while the exclusion criteria involved removing drugs with the highest side effects based on database information. Initially, the structure of the HO-1 enzyme was extracted from the Protein Data Bank. Then, using various software and servers such as Discovery Studio, YASARA Energy Minimization, and Chimera, the structures of additional ligands were extracted from the protein structure, followed by optimization of the protein structure. Based on the DrugBank and PubChem databases, drugs that could have the greatest impact were identified and screened, and then the pharmaceutical compounds were extracted and optimized using ChemBio3D and augadroo software. Molecular docking was performed using Molegro Virtual Docker 2019 software.</span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">Results:</span></span></b><span style="font-size:11.0pt"><span new="" roman="" style="font-family:" times=""> Among the pharmaceutical compounds used to interact with HO-1, the following had the highest interactions in order: NADH>alpha-Tocopherol succinate>Vitamin E > Tryptophan > Isopropyl Alcohol, with their interaction energy levels being -192.9050<-142.1080<-133.146<-95.7108<-43.6045, respectively. The number of hydrogen bonds corresponding to these compounds with HO-1 was 10, 1, 2, 2, and 3 hydrogen bonds, respectively.</span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">Conclusion:</span></span></b><span style="font-size:11.0pt"><span new="" roman="" style="font-family:" times=""> The pharmaceutical compound NADH exhibited the highest interaction with the HO-1 enzyme. The compounds alpha-Tocopherol succinate and Vitamin E showed significant interactions with the HO-1 enzyme. Tryptophan and Isopropyl Alcohol demonstrated suitable interactions with the HO-1 enzyme. HO-1 is a suitable enzyme for controlling pain and inflammation associated with TMD.</span></span></span></span></span></span><br> &nbsp; اختلالات مفصل گیجگاهی فکی, HO-1, داکینگ مولکولی, مدلسازی دارویی, مولگروویرچوال داکر Temporomandibular joint disorders, HO-1, molecular docking, drug modeling, Molegro Virtual Docker 33 43 http://sjku.muk.ac.ir/browse.php?a_code=A-10-5901-2&slc_lang=fa&sid=1 Payam Younesi Baneh پیام یونسی بانه p.younesibaneh@gmail.com 5400319475328460071866 0009-0005-2733-1496 No Kurdistan University of Medical Sciences دانشگاه علوم پزشکی کردستان hamzeh salehzadeh حمزه صالح زاده hamzeh.salehzadeh@gmail.com 5400319475328460071867 5400319475328460071867 No Kurdistan University of Medical Sciences دانشگاه علوم پزشکی کردستان Shadieh Mohammadi شادیه محمدی Shadiehmohammadi@yahoo.com 5400319475328460071868 5400319475328460071868 No Kurdistan University of Medical Sciences دانشگاه علوم پزشکی کردستان Hady Mohammadi هادی محمدی hadi.mohammadi6160@gmail.com 5400319475328460071869 0009-0007-8932-1028 Yes Kurdistan University of Medical Sciences دانشگاه علوم پزشکی کردستان Omid Zarei امید زارعی o.zarei@muk.ac.ir 5400319475328460071870 5400319475328460071870 No Kurdistan University of Medical Sciences دانشگاه علوم پزشکی کردستان