The structural description of peptide ligands bound to G protein-coupled receptors (GPCRs) is important for the discovery of new drugs and deeper understanding of the molecular mechanisms of life. Here we describe a three-stage protocol for the molecular docking of peptides to GPCRs using a set of different programs: (1) CABS-dock for docking fully flexible peptides; (2) PD2 method for the reconstruction of atomistic structures from C-alpha traces provided by CABS-dock and (3) Rosetta FlexPepDock for the refinement of protein–peptide complex structures and model scoring. We evaluated the proposed protocol on the set of seven different GPCR–peptide complexes (including one containing a cyclic peptide), for which crystallographic structures are available. We show that CABS-dock produces high resolution models in the sets of top-scored models. These sets of models, after reconstruction to all-atom representation, can be further improved by Rosetta high-resolution refinement and/or minimization, leading in most of the cases to sub-Angstrom accuracy in terms of interface root-mean-square-deviation measure.

中文翻译：

---

使用 CABS-dock 与 FlexPepDock 改进的组合将肽对接至 GPCR。

与 G 蛋白偶联受体 (GPCR) 结合的肽配体的结构描述对于新药的发现和对生命分子机制的更深入理解非常重要。在这里，我们描述了使用一组不同程序将肽分子对接到 GPCR 的三阶段协议：(1) CABS-dock 用于对接完全灵活的肽；(2) 用于从 CABS-dock 提供的 C-alpha 轨迹重建原子结构的 PD2 方法和 (3) Rosetta FlexPepDock，用于改进蛋白质 - 肽复合物结构和模型评分。我们在一组七种不同的 GPCR-肽复合物（包括一种含有环肽的复合物）上评估了提议的协议，这些复合物的晶体结构是可用的。我们展示了 CABS-dock 在得分最高的模型集中生成高分辨率模型。