The docked poses from the docking screens against the AlphaFold2 models of the σ2 and 5HT2A receptors

Though AlphaFold2 (AF2) models have had wide impact, they have had mixed success in retrospective ligand recognition. Here, we prospectively docked large libraries against unrefined AF2 models of the σ2 and 5-HT2A receptors, testing hundreds of new molecules and comparing results to docking against the experimental structures. Hit rates were high and similar for the experimental and the AF2 structures, as were affinities. The success of docking against the AF2 models was achieved despite differences in orthosteric residue conformations versus the experimental structures. Determination of the cryoEM structure for one of the more potent 5HT2A ligands from the AF2 docking revealed residue accommodations that resembled the AF2 prediction. AF2 models may sample conformations that differ from experimental structures but remain low energy and relevant for ligand discovery, extending the domain of structure-based ligand discovery. This repository contains docked poses shown in this study. The d..., , , # The docked poses from the docking screens against the AlphaFold2 models of the σ2 and 5HT2A receptors [https://doi.org/10.5061/dryad.sbcc2frf5](https://doi.org/10.5061/dryad.sbcc2frf5) This repository contains docked poses shown in the following paper. Lyu, J., Kapolka, N., Gumpper, R., Alon, A., Wang, L., Jain, M. K., ... & Roth, B. L. (2023). AlphaFold2 structures template ligand discovery. *bioRxiv*, 2023-12. The data contain 1) AlphaFold2 models of the σ2 and 5HT2A receptors used to generate these two docked poses and 2) docked poses of ZINC000866533340 in the σ2 model and Z7757 (ZINClB000002x4yW) in the 5HT2A model. ## Description of the data and file structure AF-Q5BJF2-F1-model_v1_prep.pdb is the AF2 model used for the docking against the σ2 receptor; AF-P28223-F1-model_v1_prep.pdb is the AF2 model used for the docking against the 5HT2A receptor; ZINC000866533340_af.mol2 is the docked pose of ZINC000866533340 in the σ2 model. 7757_af.mol2 is the docked pose of Z775...尽管阿尔法折叠2（AlphaFold2，简称AF2）模型已产生广泛影响，但在回顾性配体识别任务中其表现参差不齐。本研究针对σ2受体与5-羟色胺2A（5-HT2A）受体的未优化AF2模型，前瞻性地对大型化合物库开展分子对接，测试了数百种全新分子，并将对接结果与基于实验解析结构的对接结果进行对比。实验结构与AF2模型的对接命中成功率均较高且水平相近，结合亲和力亦如此。尽管正构位点残基构象与实验结构存在差异，但基于AF2模型的对接仍取得了成功。针对AF2对接筛选出的一款强效5-HT2A配体，我们解析了其冷冻电镜（cryoEM）结构，发现残基适配模式与AF2的预测结果高度相似。AF2模型能够采样出与实验结构存在差异的构象，但这些构象仍处于低能状态且可用于配体发现研究，从而拓展了基于结构的配体发现领域边界。 本数据集仓库包含本研究中展示的分子对接构象。 本仓库包含针对σ2受体与5-HT2A受体的AF2模型进行对接筛选得到的分子对接构象。 [https://doi.org/10.5061/dryad.sbcc2frf5](https://doi.org/10.5061/dryad.sbcc2frf5) 本仓库包含下述论文中展示的分子对接构象： Lyu, J., Kapolka, N., Gumpper, R., Alon, A., Wang, L., Jain, M. K., 等 & Roth, B. L. (2023). 《AlphaFold2结构指导配体发现》。*bioRxiv*, 2023-12。 本数据集包含两部分内容：1）用于生成这两组对接构象的σ2受体与5-HT2A受体的AF2模型；2）σ2模型中ZINC000866533340的对接构象，以及5-HT2A模型中Z7757（ZINClB000002x4yW）的对接构象。 数据与文件结构说明： AF-Q5BJF2-F1-model_v1_prep.pdb：用于σ2受体对接的AF2模型； AF-P28223-F1-model_v1_prep.pdb：用于5-HT2A受体对接的AF2模型； ZINC000866533340_af.mol2：ZINC000866533340在σ2模型中的对接构象文件； 7757_af.mol2：Z7757的对接构象文件（原文此处存在截断）。