Yang Yian, Qian Jiaqiang, Ming Dengming
Department of Physiology and Biophysics, School of Life Science, Fudan University, 2005 Songhu Road, Shanghai 200438, China; Mechanobiology Institute, Lv. 10 T-Lab, 5A Engineering Drive 1, 117411 Singapore.
Department of Physiology and Biophysics, School of Life Science, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
Carbohydr Res. 2015 Sep 23;414:78-84. doi: 10.1016/j.carres.2015.07.013. Epub 2015 Jul 23.
Protein-carbohydrate interactions (PCIs) involve a variety of essential biological processes such as cell recognition and migration, metabolism processes and immunological reactions, which are important for securing functions of living organisms. Due to the polysaccharide structural diversity and dynamics flexibility, PCIs can be very difficult for experimental measurement and computer prediction. Here we report a simple method for docking polysaccharide to proteins whose binding pockets have a Tryptophan box. The method samples polysaccharide conformations using constraint conditions imposed by the box, evaluate the conformation energies based on a knowledge-based potential function, and finds the best docking structures using the conventional Monte Carlo simulated annealing technique. We applied the method to dock polysaccharides with 2 to 4 monomers to three carbohydrate-binding proteins, whose pockets have clear aromatic residue-defined binding channels. The predictions found correct carbohydrate binding conformations with atomic RMSD of 1.1-1.6 Å from X-ray crystal structures. The calculation can be performed in ordinary PC and only cost a couple of minutes for a single docking. Our method, when combined with other docking programs, provides a reliable start conformation for further accurate simulation of PCIs.
蛋白质 - 碳水化合物相互作用（PCIs）涉及多种重要的生物过程，如细胞识别与迁移、代谢过程以及免疫反应，这些对于维持生物体的功能至关重要。由于多糖结构的多样性和动态灵活性，PCIs的实验测量和计算机预测都极具挑战性。在此，我们报告一种将多糖对接至具有色氨酸盒的蛋白质结合口袋的简单方法。该方法利用色氨酸盒施加的约束条件对多糖构象进行采样，基于基于知识的势函数评估构象能量，并使用传统的蒙特卡罗模拟退火技术找到最佳对接结构。我们将该方法应用于将含有2至4个单体的多糖对接至三种碳水化合物结合蛋白，这些蛋白的口袋具有明确的由芳香族残基定义的结合通道。预测结果找到了与X射线晶体结构的原子均方根偏差（RMSD）为1.1 - 1.6 Å的正确碳水化合物结合构象。该计算可在普通个人电脑上进行，单次对接仅需几分钟。我们的方法与其他对接程序相结合，可为进一步精确模拟PCIs提供可靠的起始构象。
