Molecular Dynamics (MD) Simulation Data: Taurocholic Acid Transportation by OSTα/OSTβ

Human OSTα/OSTβ is a vital bile acid (BA) transporter. This study elucidated its structure and transport mechanism using cryo-EM and molecular dynamics.Cryo-EM revealed OSTα/OSTβ as a novel "dimer of heterodimers," with an OSTα homodimer core and peripheral OSTβs. OSTα, with a GPCR-fold, features a BA recognition site involving a cysteine-rich loop and transmembrane helices. A positive cavity facilitates BA translocation.Molecular dynamics (MD) simulations, including well-tempered metadynamics (wt-MetaD), detailed the taurocholic acid (TCA) transport pathway. It involves a "head-down" to "head-up" flip across the membrane, moving through intermediate states within a positive cavity. Polar residues guide the BA towards the extracellular side.This repository contains molecular dynamics (MD) simulation data aimed at elucidating the transportation of taurocholic acid (TCA) by the OSTα/OSTβ protein complex embedded within a POPC lipid bilayer.Directory StructureMD_system_parameters.csv: This file details the system composition and the simulation box dimensions used for all MD simulations.POPC_CMD/: This directory contains data from Conventional Molecular Dynamics (CMD) simulations.POPC_MetaD/: This directory contains data from Metadynamics (MetaD) simulations.Conventional Molecular Dynamics (CMD) Data (POPC_CMD/)This directory includes three independent conventional molecular dynamics simulation runs. These simulations provide insights into the dynamic behavior of the system under standard conditions.Files:runX_0ns.pdb: Initial PDB (Protein Data Bank) coordinate file for run X (where X is 1, 2, or 3) at 0 nanoseconds. These files represent the starting configuration for each simulation.runX_500ns.pdb: Final PDB coordinate file for run X (where X is 1, 2, or 3) after 500 nanoseconds of simulation. These files capture the system's configuration at the end of each run.runX_all_trj.xtc: Compressed trajectory file for the entire duration of run X (where X is 1, 2, or 3). These files contain atomic coordinates over time, allowing for detailed analysis of molecular motion and interactions throughout the simulation.Metadynamics (MetaD) Data (POPC_MetaD/)This directory includes data from a Metadynamics simulation. Metadynamics is a powerful enhanced sampling technique often used to explore complex free energy landscapes, particularly relevant for understanding transport processes and conformational changes.Files:Meta_ini.pdb: Initial PDB coordinate file used for the Metadynamics simulation. This represents the starting configuration for the enhanced sampling run.Meta_trj.xtc: Compressed trajectory file for the Metadynamics simulation. This trajectory can be analyzed to reconstruct free energy profiles and pathways related to TCA transportation.人源OSTα/OSTβ是一类重要的胆汁酸（bile acid, BA）转运蛋白。本研究借助冷冻电镜（cryo-EM）与分子动力学（molecular dynamics）技术解析了其结构与转运机制。 冷冻电镜结果显示，OSTα/OSTβ为一种新型的“异二聚体二聚体”结构，其核心为OSTα同源二聚体，外周结合OSTβ亚基。OSTα具有G蛋白偶联受体折叠（GPCR-fold）结构，其胆汁酸识别位点包含一个富含半胱氨酸的环与跨膜螺旋，其带正电的空腔可介导胆汁酸的跨膜转运。 分子动力学（MD）模拟（含恒温元动力学（well-tempered metadynamics, wt-MetaD））详细阐释了牛磺胆酸（taurocholic acid, TCA）的转运通路：该通路涉及牛磺胆酸在膜内发生“头朝下”至“头朝上”的构象翻转，并经由带正电空腔内的中间状态完成转运，极性残基可引导胆汁酸向细胞膜外侧移动。 本仓库存储的分子动力学模拟数据，旨在解析嵌入于1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱（POPC）脂质双分子层中的OSTα/OSTβ蛋白复合物对牛磺胆酸（TCA）的转运过程。 ### 目录结构 1. `MD_system_parameters.csv`：该文件记录了所有分子动力学模拟所用的体系组成与模拟盒尺寸参数。 2. `POPC_CMD/`：该目录存储常规分子动力学（Conventional Molecular Dynamics, CMD）模拟数据。 3. `POPC_MetaD/`：该目录存储元动力学（Metadynamics, MetaD）模拟数据。 #### 常规分子动力学数据（`POPC_CMD/`） 该目录包含3组独立的常规分子动力学模拟运行结果，可用于分析标准条件下体系的动态行为。 文件说明： - `runX_0ns.pdb`：第X组模拟（X取值为1、2、3）初始时刻（0纳秒）的蛋白质数据银行（Protein Data Bank, PDB）坐标文件，即各组模拟的初始构型。 - `runX_500ns.pdb`：第X组模拟运行500纳秒后的最终PDB坐标文件，记录了模拟结束时的体系构型。 - `runX_all_trj.xtc`：第X组模拟全时长的压缩轨迹文件（XTC格式，X取值为1、2、3），包含随时间变化的原子坐标，可用于详细分析模拟全程的分子运动与相互作用。 #### 元动力学（MetaD）数据（`POPC_MetaD/`） 该目录包含一组元动力学模拟数据。元动力学是一种高效的增强采样技术，常用于探索复杂的自由能景观，尤其适用于解析转运过程与构象变化。 文件说明： - `Meta_ini.pdb`：元动力学模拟所用的初始PDB坐标文件，即该增强采样运行的初始构型。 - `Meta_trj.xtc`：元动力学模拟的压缩轨迹文件，可通过该轨迹重构与TCA转运相关的自由能分布与通路。