All-atom molecular dynamics simulation and rate calculation for norepinephrine binding beta adrenergic receptor

This dataset is for the manuscript \"A multiscale predictive digital twin for neurocardiac modulation\". We utilized all-atom molecular dynamics (MD) simulations to predict the affinities as well as association and dissociation rates of norepinephrine (NE) with the beta-2 adrenergic receptor (β2AR). Calculations were done for both cationic (+) and neutral (0) forms of NE. An active-state β2AR model based on its crystal structure PDB ID: 4LDO was used with the flexible intracellular loop 3 (ICL3) truncated to 3 residues. ROSETTALIGAND was used for docking NE(+) and NE(0) to the receptor's orthosteric ligand binding site with one of the top scoring models used for MD simulations. MD simulation systems of the NE(+) or NE(0) bound β2AR receptor embedded in a palmitoyloleoylphosphatidylcholine (POPC) bilayer solvated by aqueous 0.15 M NaCl was generated using CHARMM-GUI membrane builder. MD simulations were run with NAMD in the NPT ensemble at 310 K and 1 atm pressure using CHARMM36m force fie..., ,本数据集配套手稿《用于神经心脏调节的多尺度预测性数字孪生》（A multiscale predictive digital twin for neurocardiac modulation）。本研究采用全原子分子动力学（all-atom molecular dynamics, MD）模拟，预测去甲肾上腺素（norepinephrine, NE）与β2肾上腺素能受体（beta-2 adrenergic receptor, β2AR）的结合亲和力、缔合速率与解离速率。计算涵盖了去甲肾上腺素的阳离子（+）与中性（0）两种构型。本研究使用基于晶体结构（蛋白质数据库[Protein Data Bank, PDB]编号4LDO）构建的激活态β2肾上腺素能受体模型，并将其柔性的细胞内环3（intracellular loop 3, ICL3）截断至3个氨基酸残基。借助ROSETTALIGAND将NE(+)与NE(0)对接至受体的正位配体结合位点（orthosteric ligand binding site），并选取得分位列前茅的模型之一开展后续分子动力学模拟。使用CHARMM-GUI膜构建工具（CHARMM-GUI membrane builder）构建嵌入棕榈酰油酰磷脂酰胆碱（palmitoyloleoylphosphatidylcholine, POPC）双分子层、并经0.15 M氯化钠水溶液溶剂化的NE(+)或NE(0)结合型β2肾上腺素能受体模拟体系。模拟体系采用NAMD软件，在NPT系综、310 K、1 atm压强条件下运行，力场采用CHARMM36m……