MD simulations of P-glycoprotein started from three different crystal strucures: 3G5U, 4M1M and 4KSB

Molecular simulations of mouse P-glycoprotein started from three different crystal structures with PDB IDs corresponding to 3G5U, 4KSB and 4M1M. The protein was transferred to POPC/cholesterol bilayer, followed by energy minimization and 10 ns equilibration period. All the simulations were performed in Gromacs 3.3.3 in conjunction with GROMOS54a7 force field at 300 K and pressure of 1 bar. Each system was run in triplicates for 200 ns.

The uploaded fileset contains:
- MD protocol used to run simulations for 3G5U, 4M1M and 4KSB systems;

- Example input file for a production run for each system (3G5U_run1.mdp, 4M1M_run1.mdp, 4KSB_run1.mdp);

- System topologies (3G5U_memb.top, 4M1M_memb.top, 4KSB_memb.top) and relevant parameter files (3g5u.itp, 4m1m.itp, 4ksb.itp, CLR.itp, POPC.itp, vdw_OML_CH3L.itp);

- Set of three trajectories containing membrane-embedded P-glycoprotein with 1000 frames for each simulated system (snapshots printed every 200 ps);

- Movies generated from each trajectory with a more detailed description provided in Movie_Legends.pdf;

- Model data calculated using principal component analysis method, including the covariance matrices, for each replica (3G5U1-3.eda.npz, 4KSB1-3.eda.npz, 4M1M1-3.eda.npz) and for the concatenated trajectory containing all 9 replicas (3G5U_4KSB_4M1M.eda.npz). The files containing data for the transmembrane domain only have the tmd prefix. These models can be further explored in ProDy package by using loadModel() function.

- Figures representing cholesterol distributions in the upper (dark violet) and lower leaflets (light violet) in all three systems at the beginning and at the end of each simulation.

以对应PDB（Protein Data Bank）编号3G5U、4KSB和4M1M的三种不同晶体结构为初始构象，开展小鼠P-糖蛋白（P-glycoprotein）的分子模拟。将该蛋白嵌入POPC/胆固醇双层膜体系中，随后进行能量最小化与10 ns平衡模拟。所有模拟均采用Gromacs 3.3.3软件结合GROMOS54a7力场完成，模拟参数设置为300 K温度、1 bar压强。每个体系均设置三次重复实验，总模拟时长为200 ns。

本次上传的文件集包含：
- 用于3G5U、4M1M及4KSB体系模拟的分子动力学（MD, Molecular Dynamics）流程脚本；
- 各体系生产模拟的示例输入文件（3G5U_run1.mdp、4M1M_run1.mdp及4KSB_run1.mdp）；
- 体系拓扑文件（3G5U_memb.top、4M1M_memb.top、4KSB_memb.top）及相关参数文件（3g5u.itp、4m1m.itp、4ksb.itp、CLR.itp、POPC.itp、vdw_OML_CH3L.itp）；
- 三套膜嵌入型P-糖蛋白的模拟轨迹文件，每个轨迹包含1000帧快照，快照采集间隔为200 ps；
- 基于各轨迹生成的可视化动画，详细说明详见Movie_Legends.pdf；
- 采用主成分分析（PCA, Principal Component Analysis）方法计算得到的模型数据，包含各重复实验的协方差矩阵（3G5U1-3.eda.npz、4KSB1-3.eda.npz、4M1M1-3.eda.npz），以及包含全部9次重复实验的合并轨迹数据集（3G5U_4KSB_4M1M.eda.npz）。仅针对跨膜结构域的数据集以tmd作为前缀命名。此类数据可通过ProDy软件包的loadModel()函数进行后续分析。
- 展示三个体系在各模拟起始与结束阶段，上层膜小叶（深紫色）与下层膜小叶（浅紫色）中胆固醇分布情况的图表。