شبیه‌سازی دینامیک مولکولی اضافه شدن رشته‌ی PAS به داروی پپتیدی G-CSF و پیشنهاد توالی جدید برای رشته‌ی PAS به منظور بهبود عمل‌کرد داروی مورد نظر

نوع مقاله: مقاله کامل پژوهشی

نویسندگان

1 کارشناس ارشد مهندسی مکانیک، گروه تبدیل انرژی، دانشکده‌ی مهندسی مکانیک، دانشگاه صنعتی شریف، تهران

2 دانشیار، گروه تبدیل انرژی، دانشکده‌ی مهندسی مکانیک، دانشگاه صنعتی شریف، تهران

10.22041/ijbme.2018.81637.1324

چکیده

در مطالعات اخیر، PASylation به عنوان یک روش موثر به منظور افزایش نیمه‌عمر داروهای پروتئینی و جایگزینی مناسب برای PEGylation مطرح شده است. در این روش، یک رشته‌ی به مراتب زیست‌سازگارتر و متشکل از پلیمرهای طبیعی، شامل پرولین، آلانین و سرین، که به اختصار به آن رشته‌ی PAS گفته می­شود، برای بهبود مشخصه­های دارو مورد استفاده قرار می­گیرد. در این مقاله، برخی از مشخصه­های داروی G-CSF، نظیر میانگین توانی فاصله‌ی اتمی (RMSD)، حجم هیدرودینامیکی، انرژی کل و میزان آب­دوستی پروتئین مورد بررسی قرار گرفته است. در این راستا، خواص مختلف داروی پروتئینی متصل به رشته‌ی PAS برای سه طول مختلف رشته‌ی مورد نظر (طول­های 210، 420 و 630) مورد بحث و بررسی قرار گرفته است. نتایج به دست آمده بیان‌گر این نکته است که با اتصال رشته‌ی PAS به داروی پروتئینی، حجم هیدرودینامیکی آن افزایش یافته و به واسطه‌ی آن نیمه‌عمر دارو نیز افزایش می­یابد. در نهایت، با در نظر داشتن نتایج به دست آمده در این قسمت، یک توالی اصلاح‌شده برای رشته‌ی PAS مورد نظر پیشنهاد شده است.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

Molecular Dynamics Simulation of PASylated G-CSF and Proposing a Modified PAS String Sequence in order to Improve Drug’s Properties

نویسندگان [English]

  • Abbas Gholami 1
  • Amir Shamloo 2
1 MSc Graduated, Mechanical Engineering Department, Sharif University of Technology, Tehran, Iran
2 Associate Professor, Mechanical Engineering Department, Sharif University of Technology, Tehran, Iran
چکیده [English]

PASylation is a new and effective way to increase the half-life of pharmaceutical proteins. This method is an alternative of PEGylaion and uses the natural polymers of Proline, Alanine, and Serine (PAS) amino acids in its structure. In this paper, we have studied the pharmacokinetic properties of PASylated Granulocyte-colony stimulating factor (G-CSF) using Molecular Dynamics (MD) simulation for three different PAS strings length 210, 420 and 630. We studied several important mechanical quantities involving in enhancing half-life time of the conjugated protein like root-mean-square distance (RMSD), hydrodynamic volume, protein total energy and its hydrophilicity and we found out volume expansion, increase in hydrophilicity amount and coil structure in PASylation are main mechanical properties influencing half-life time. We also found out that RMSD will be modified by PASylation while energy level shows erratic behavior examining the mentioned residues properties, we have also offered a modified sequence for PAS string according to the importance of different parameters in PAS string’s function.

کلیدواژه‌ها [English]

  • Pegylation
  • Pasylation
  • G-CSF
  • Half-Life
  • Hydrodynamic Volume
  • Molecular Dynamic

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