In this study, the effectiveness of PASylation in enhancing the potency and plasma half‐life of pharmaceutical proteins has been accredited as an alternative technique to the conventional methods such as PEGylation. Proline, alanine, and serine (PAS) chain has shown some advantages including biodegradability improvement and plasma half‐life enhancement while lacking immunogenicity or toxicity. Although some experimental studies have been performed to find the mechanism behind PASylation, the detailed mechanism of PAS effects on the pharmaceutical proteins has remained obscure, especially at the molecular level. In this study, the interaction of interferon α‐2a (IFN) and PAS chain is investigated using molecular dynamics simulation method. Several important parameters including secondary structure, root‐mean‐square distance, and solvent accessible surface area to investigate the stability, bioavailability, and bioactivity of the PASylated protein are studied. The results demonstrate that IFN conformation is not affected critically through PASylation while it results in improvement of the protein stability and bioactivity. Therefore, PASylation can be considered as a proper biological alternative technique to increase the plasma half‐life of the biopharmaceutical proteins through enlarging apparent volume. The proposed simulation represents a computational approach that would provide a basis for the study of PASylated pharmaceutical proteins for different future applications.

中文翻译：

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PASylation增强了干扰素α-2a的稳定性，效能和血浆半衰期：分子动力学模拟。

在这项研究中，PASylation在增强药物蛋白的效力和血浆半衰期方面的有效性已被认可为传统方法（例如PEG化）的替代技术。脯氨酸，丙氨酸和丝氨酸（PAS）链显示出一些优势，包括可生物降解性提高和血浆半衰期提高，同时缺乏免疫原性或毒性。尽管已经进行了一些实验研究来发现PASylation背后的机制，但是PAS对药物蛋白的作用的详细机制仍然不清楚，尤其是在分子水平上。在这项研究中，使用分子动力学模拟方法研究了干扰素α-2a（IFN）与PAS链的相互作用。几个重要参数，包括二级结构，均方根距离，和溶剂可及的表面积来研究PASylated蛋白的稳定性，生物利用度和生物活性。结果表明，IFN构象不会受到PASylation的严重影响，而可导致蛋白稳定性和生物活性的提高。因此，PASylation可以被认为是通过增加表观体积来延长生物制药蛋白的血浆半衰期的适当生物替代技术。拟议的模拟代表了一种计算方法，该方法将为研究PASylated药物蛋白用于不同未来应用提供基础。结果表明，IFN构象不会受到PASylation的严重影响，而可导致蛋白稳定性和生物活性的提高。因此，PASylation可以被认为是通过增加表观体积来延长生物制药蛋白的血浆半衰期的适当生物替代技术。拟议的模拟代表了一种计算方法，该方法将为研究PASylated药物蛋白用于不同未来应用提供基础。结果表明，IFN构象不会受到PASylation的严重影响，而可导致蛋白稳定性和生物活性的提高。因此，PASylation可以被认为是通过增加表观体积来延长生物制药蛋白的血浆半衰期的适当生物替代技术。拟议的模拟代表了一种计算方法，该方法将为研究PASylated药物蛋白用于不同未来应用提供基础。