Voltage‐dependent anion channel (VDAC) is the primary conduit for regulated passage of ions and metabolites into and out of a mitochondrion. Calculating the solvation free energy for VDAC is crucial for understanding its stability, function, and interactions within the cellular environment. In this article, numerical schemes for computing the total solvation free energy for VDAC—comprising electrostatic, ideal gas, and excess free energies plus the nonpolar energy—are developed based on a nonuniform size modified Poisson–Boltzmann ion channel (nuSMPBIC) finite element solver along with tetrahedral meshes for VDAC proteins. The current mesh generation package is also updated to improve mesh quality and accelerate mesh generation. A VDAC Solvation Free Energy Calculation (VSFEC) package is then created by integrating these schemes with the updated mesh package, the nuSMPBIC finite element package, the PDB2PQR package, and the OPM database, as well as one uniform SMPBIC finite element package and one Poisson–Boltzmann ion channel (PBIC) finite element package. With the VSFEC package, many numerical experiments are made using six VDAC proteins, eight ionic solutions containing up to four ionic species, including ATP4− and Ca2+, two reference states, different boundary values, and different permittivity constants. The test results underscore the importance of considering nonuniform ionic size effects to explore the varying patterns of the total solvation free energy, and demonstrate the high performance of the VSFEC package for VDAC solvation free energy calculation.

中文翻译：

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通过非均匀尺寸修正泊松-玻尔兹曼离子通道模型计算 VDAC 溶剂化自由能


电压依赖性阴离子通道 （VDAC） 是离子和代谢物进出线粒体的调节通道的主要通道。计算 VDAC 的溶剂化自由能对于了解其稳定性、功能和细胞环境中的相互作用至关重要。在本文中，基于非均匀尺寸修正泊松-玻尔兹曼离子通道 （nuSMPBIC） 有限元求解器以及 VDAC 蛋白质的四面体网格，开发了用于计算 VDAC 总溶剂化自由能的数值方案，包括静电、理想气体和过量自由能以及非极性能量。当前的网格生成包也进行了更新，以提高网格质量并加快网格生成速度。然后，通过将这些方案与更新的网格包、nuSMPBIC 有限元包、PDB2PQR 包和 OPM 数据库以及一个统一的 SMPBIC 有限元包和一个泊松-玻尔兹曼离子通道 （PBIC） 有限元包集成，创建 VDAC 溶剂化自由能量计算 （VSFEC） 包。使用 VSFEC 软件包，使用 6 种 VDAC 蛋白、8 种离子溶液（包含多达 4 种离子物质，包括 ATP4− 和 Ca2+）、两种参考状态、不同的边界值和不同的介电常数进行许多数值实验。测试结果强调了考虑非均匀离子尺寸效应以探索总溶剂化自由能的不同模式的重要性，并证明了 VSFEC 包在 VDAC 溶剂化自由能计算中的高性能。