Polyamine-dependent metabolic shielding regulates alternative splicing

Abbreviations: SF3A3: Splicing Factor 3a Subunit 3 CK1: Casein kinase 1 PUT: Putrescine SPD: Spermidine, SPM: Spermine, BENSpm: N1,N11-bis(ethyl)norspermine Computational Data: 0-molecular_docking (best binding poses) • SF3A3: binary complexes between Splicing Factor 3a Subunit 3 and the four polyamines (putrescine, spermidine, spermine, N1,N11-bis(ethyl)norspermine). 10 best poses for each system in PDB format. • SF3A3_CK1: ternary complexes between Splicing Factor 3a Subunit 3, Casein kinase 1 and the four polyamines (putrescine, spermidine, spermine, N1,N11-bis(ethyl)norspermine). Best pose for each system in PDB format. 1-conventional_MD (molecular dynamics simulations) • SF3A3: binary complexes between Splicing Factor 3a Subunit 3 and the four polyamines (putrescine, spermidine, spermine, N1,N11-bis(ethyl)norspermine). 100 frames in PDB format collected from 10 independent simulations per system with frame frequency 1/10 ns. - salt_bridge_analysis: interatomic distances in Å between the nitrogen of each ammonium group for each polyamine, and the center of mass of the carboxylate oxygens of each Glu sidechain of the acidic surrounding the phosphorylatable serines. • SF3A3_CK1: ternary complexes between Splicing Factor 3a Subunit 3, Casein kinase 1 and the four polyamines (putrescine, spermidine, spermine, N1,N11-bis(ethyl)norspermine). 10 frames in PDB format collected from one simulation per system with frame frequency 1/10 ns. 2-REUS_MD: (Hamiltonian Replica Exchange Umbrella Sampling simulations) • SF3A3_PUT: (Un)binding free energy profile of putrescine to SF3A3. • SF3A3_SPD: (Un)binding free energy profile of spermidine to SF3A3. • SF3A3_SPM: (Un)binding free energy profile of spermine to SF3A3. • SF3A3_BENSpm: (Un)binding free energy profile of N1,N11-bis(ethyl)norspermine to SF3A3. • peptide_SPD: (Un)binding free energy profile of spermidine to SF3A3 cognate peptide. • peptide_SPM: (Un)binding free energy profile of spermine to SF3A3 cognate peptide. Each folder contains the metadata file (meta) defining the simulation windows and biasing potential for each system, the raw data for each simulation window (clean_xx.dat) and an execution script for computing the potentials of mean force (PMF) with the Weighted Histogram Analysis Method as implemented in the WHAM program (run_wham.sh).缩写列表： SF3A3：剪接因子3a亚基3（Splicing Factor 3a Subunit 3） CK1：酪蛋白激酶1（Casein kinase 1） PUT：腐胺（Putrescine） SPD：亚精胺（Spermidine） SPM：精胺（Spermine） BENSpm：N1,N11-二乙基去甲精胺（N1,N11-bis(ethyl)norspermine） 计算数据： 0. 分子对接（molecular_docking，最佳结合构象） • SF3A3：剪接因子3a亚基3与4种多胺（腐胺、亚精胺、精胺、N1,N11-二乙基去甲精胺）组成的二元复合物。每个体系获取10个最佳结合构象，格式为PDB。 • SF3A3_CK1：剪接因子3a亚基3、酪蛋白激酶1与上述4种多胺组成的三元复合物。每个体系获取1个最佳结合构象，格式为PDB。 1. 常规分子动力学模拟（conventional_MD，分子动力学模拟） • SF3A3：剪接因子3a亚基3与上述4种多胺组成的二元复合物。每个体系通过10次独立模拟，每10纳秒采集1帧，共获取100帧PDB格式文件。 - 盐桥分析（salt_bridge_analysis）：各多胺的每个铵基氮原子，与可磷酸化丝氨酸周围酸性区域内各谷氨酸侧链羧基氧原子的质心之间的原子间距离，单位为埃（Å）。 • SF3A3_CK1：剪接因子3a亚基3、酪蛋白激酶1与上述4种多胺组成的三元复合物。每个体系通过1次模拟，每10纳秒采集1帧，共获取10帧PDB格式文件。 2. 哈密顿副本交换伞形采样分子动力学模拟（REUS_MD，Hamiltonian Replica Exchange Umbrella Sampling simulations） • SF3A3_PUT：腐胺与剪接因子3a亚基3的结合/去结合自由能分布曲线 • SF3A3_SPD：亚精胺与剪接因子3a亚基3的结合/去结合自由能分布曲线 • SF3A3_SPM：精胺与剪接因子3a亚基3的结合/去结合自由能分布曲线 • SF3A3_BENSpm：N1,N11-二乙基去甲精胺与剪接因子3a亚基3的结合/去结合自由能分布曲线 • peptide_SPD：亚精胺与剪接因子3a亚基3同源肽的结合/去结合自由能分布曲线 • peptide_SPM：精胺与剪接因子3a亚基3同源肽的结合/去结合自由能分布曲线 每个文件夹均包含以下文件：定义各体系模拟窗口与偏置势能的元数据文件（meta）、各模拟窗口的原始数据文件（clean_xx.dat），以及采用加权直方图分析方法（Weighted Histogram Analysis Method，WHAM）实现的平均力势（Potentials of Mean Force，PMF）的计算脚本（run_wham.sh）。