Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland.
Intercollegiate Faculty of Biotechnology of UG and MUG, ul. Abrahama 58, 80-307 Gdańsk, Poland.
J Chem Inf Model. 2021 Sep 27;61(9):4475-4485. doi: 10.1021/acs.jcim.1c00664. Epub 2021 Sep 8.
Docking glycosaminoglycans (GAGs) has been challenging because of the complex nature of these long periodic linear and negatively charged polysaccharides. Although standard docking tools like Autodock3 are successful when docking GAGs up to hexameric length, they experience challenges to properly dock longer GAGs. Similar limitations concern other docking approaches typically developed for docking ligands of limited size to proteins. At the same time, most of more advanced docking approaches are challenging for a user who is inexperienced with complex methodologies. In this work, we evaluate the binding energies of complexes with different lengths of GAGs using all-atom molecular dynamics simulations. Based on this analysis, we propose a new docking protocol for long GAGs that consists of conventional docking of short GAGs and further elongation with the use of a coarse-grained representation of the GAG parts not being in direct contact with its protein receptor. This method automated by a simple script is straightforward to use within the Autodock3 framework but also useful in combination with other standard docking tools. We believe that this method with some minor case-specific modifications could also be used for docking other linear charged polymers.
对接糖胺聚糖（GAGs）具有挑战性，因为这些长周期线性和带负电荷的多糖具有复杂的性质。尽管像 Autodock3 这样的标准对接工具在对接长达六聚体长度的 GAGs 时非常成功，但它们在正确对接更长的 GAGs 时会遇到挑战。其他通常为对接有限大小配体到蛋白质的对接方法也存在类似的限制。与此同时，对于没有复杂方法经验的用户来说，大多数更先进的对接方法都具有挑战性。在这项工作中，我们使用全原子分子动力学模拟评估了具有不同长度 GAGs 的复合物的结合能。基于此分析，我们提出了一种用于长 GAGs 的新对接方案，该方案由短 GAGs 的常规对接和使用粗粒度表示法进一步延伸组成，该表示法不与与其蛋白质受体直接接触的 GAG 部分。通过一个简单的脚本实现自动化，该方法可直接在 Autodock3 框架内使用，也可与其他标准对接工具结合使用。我们相信，这种方法经过一些特定情况的微小修改，也可用于对接其他线性带电聚合物。
