Unraveling the structure of lectin–carbohydrate complexes is vital for understanding key biological recognition processes and development of glycomimetic drugs. Molecular Docking application to predict them is challenging due to their low affinity, hydrophilic nature and ligand conformational diversity. In the last decade several strategies, such as the inclusion of glycan conformation specific scoring functions or our developed solvent-site biased method, have improved carbohydrate docking performance but significant challenges remain, in particular, those related to receptor conformational diversity. In the present work we have analyzed conventional and solvent-site biased autodock4 performance concerning receptor conformational diversity as derived from different crystal structures (apo and holo), Molecular Dynamics snapshots and Homology-based models, for 14 different lectin–monosaccharide complexes. Our results show that both conventional and biased docking yield accurate lectin–monosaccharide complexes, starting from either apo or homology-based structures, even when only moderate (45%) sequence identity templates are available. An essential element for success is a proper combination of a middle-sized (10–100 structures) conformational ensemble, derived either from Molecular dynamics or multiple homology model building. Consistent with our previous works, results show that solvent-site biased methods improve overall performance, but that results are still highly system dependent. Finally, our results also show that docking can select the correct receptor structure within the ensemble, underscoring the relevance of joint evaluation of both ligand pose and receptor conformation.

中文翻译：

---

有效利用X射线信息，同源性建模，分子动力学和基于知识的对接技术来预测蛋白质-单糖复合物

解开凝集素-碳水化合物复合物的结构对于理解关键的生物识别过程和拟糖药物的开发至关重要。由于它们的低亲和力，亲水性和配体构象多样性，使用分子对接技术预测它们具有挑战性。在过去的十年中，几种策略，例如包含聚糖构象特异性评分功能或我们开发的溶剂位点偏倚方法，均改善了碳水化合物的对接性能，但仍然存在重大挑战，尤其是与受体构象多样性有关的挑战。在目前的工作中，我们分析了与受体构象多样性有关的传统的和溶剂位偏的autodock4性能，这些性能源自于不同的晶体结构（载脂蛋白和全息），针对14种不同的凝集素-单糖复合物的分子动力学快照和基于同源性的模型。我们的结果表明，即使只有中等程度（45％）的序列同一性模板可用，传统的和有偏的对接都能从基于载脂蛋白或基于同源性的结构中产生准确的凝集素-单糖复合物。成功的基本要素是中型（10–100个结构）构象集合的适当组合，该集合可以从分子动力学或多个同源性模型构建中获得。与我们之前的工作一致，结果表明溶剂偏倚的方法可改善整体性能，但结果仍与系统高度相关。最后，我们的结果还表明，对接可以选择整体中正确的受体结构，