Simulations for benchmarking interactive flexible molecular docking for Virtual Reality in DockIT

This series of flexible-receptor docking simulations were developed to benchmark interactive docking performance in DockIT. There are seven test cases comprising a varying range of atoms up to approximately 92,000. The seven pairs are detailed below. Molecule Pair (Receptor-Ligand) Receptor created from MD Simulation Number of Atoms in Receptor Number of Atoms in Ligand GGG–GLTM Yes 3431 20 HDAC–OJ Yes 5478 41 OMP–MLTS Yes 5737 45 2X_OMP–2X_OMP Created from OMP 11474 11474 4X_OMP–4X_OMP Created from 2X_OMP 22948 22948 8X_OMP–8X_OMP Created from 4X_OMP 45896 45896 16X_OMP–16X_OMP Created from 8X_OMP 91792 91792 The first three pairs for benchmarking are molecular structure files downloaded from the PDB. Molecular Dynamics Simulations are performed on the receptors to obtain a molecular dynamics trajectory. The trajectories and original PDB files are used to compute the eigen vectors and eigen values following the approach as detailed here: https://colab.research.google.com/drive/1i7db2LINovZGhvQJmls9oOqpfYnOofKf?usp=sharing Further details on the simulations for Maltose Binding Protein (OMP above) and Glutamine Binding Protein (GGG above) can be found here https://doi.org/10.1021/acs.jcim.9b00112. For HDAC please refer to https://pubs.acs.org/doi/10.1021/acs.jchemed.4c01347. For the purposes of benchmarking larger structures, the OMP structure from above is extended by copying the information created for OMP. We constructed 2X_OMP and 8X_OMP by stacking respectively OMP and 4X_OMP molecules along their first principal axis. Whereas we constructed 4X_OMP and 16X_OMP by stacking respectively 2X_OMP and 8X_OMP molecules along their second principal axis.本系列柔性受体对接模拟旨在为DockIT平台中的交互式对接性能提供基准评测。本次测试共包含7组测试用例，原子数量跨度较大，最高约为92000。7组分子对详情如下： 1. GGG–GLTM：受体来源为分子动力学（MD, Molecular Dynamics）模拟，受体原子数3431，配体原子数20 2. HDAC–OJ：受体来源为分子动力学（MD, Molecular Dynamics）模拟，受体原子数5478，配体原子数41 3. OMP–MLTS：受体来源为分子动力学（MD, Molecular Dynamics）模拟，受体原子数5737，配体原子数45 4. 2X_OMP–2X_OMP：受体来源为OMP，受体原子数11474，配体原子数11474 5. 4X_OMP–4X_OMP：受体来源为2X_OMP，受体原子数22948，配体原子数22948 6. 8X_OMP–8X_OMP：受体来源为4X_OMP，受体原子数45896，配体原子数45896 7. 16X_OMP–16X_OMP：受体来源为8X_OMP，受体原子数91792，配体原子数91792 本次基准测试的前3组分子对为从PDB（Protein Data Bank，蛋白质数据库）下载的分子结构文件。研究人员对受体开展分子动力学模拟以获取分子动力学轨迹，并基于该轨迹与原始PDB文件，按照下述链接中详述的方法计算特征向量与特征值：https://colab.research.google.com/drive/1i7db2LINovZGhvQJmls9oOqpfYnOofKf?usp=sharing 关于麦芽糖结合蛋白（即上述OMP）与谷氨酰胺结合蛋白（即上述GGG）的模拟详情，可参阅下述文献：https://doi.org/10.1021/acs.jcim.9b00112。有关HDAC的相关信息，请参考：https://pubs.acs.org/doi/10.1021/acs.jchemed.4c01347。 为实现更大尺寸结构的基准测试，我们通过复制原有OMP的结构信息对其进行扩增。其中，2X_OMP与8X_OMP分别通过沿第一主轴线堆叠OMP与4X_OMP分子构建；4X_OMP与16X_OMP则分别通过沿第二主轴线堆叠2X_OMP与8X_OMP分子构建。