Mixing MARTINI: electrostatic coupling in hybrid atomistic-coarse-grained biomolecular simulations.
Mixing MARTINI: electrostatic coupling in hybrid atomistic-coarse-grained biomolecular simulations.
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DOI：
10.1021/jp311533p
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发表时间：
2013-04
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影响因子：
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通讯作者：
T. Wassenaar;Helgi I. Ingólfsson;Marten Prieß;S. Marrink;Lars V. Schäfer
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作者：
T. Wassenaar;Helgi I. Ingólfsson;Marten Prieß;S. Marrink;Lars V. Schäfer
混合分子动力学模拟嵌入在粗粒度（CG）环境中的原子（AA）溶质可以大大减少计算成本相对于完全原子模拟。然而，连接两个层次的分辨率是一个重大挑战，包括相关的相互作用的平衡描述。这对于极性溶剂如水尤其如此，其屏蔽静电相互作用，因此需要AA和CG子系统之间的明确静电耦合。在这里，我们提出并严格测试计算效率的混合AA/CG模型。我们结合了Gromos原子力场和MARTINI粗粒力场。制定静电耦合，最近开发的CG水模型与明确的静电相互作用：极化MARTINI水模型和宝马模型。混合模型被发现是敏感的AA-CG静电耦合的强度，这是通过调整的相对介电常数εr（AA-CG）。潜在的平均力（PMFs）之间的氨基酸侧链类似物在水中和分区之间的非极性溶剂和水的不带电荷的氨基酸侧链类似物的游离的arrhopies的对显示显着差异的混合动力模拟和完全AA或CG模拟，特别是带电和极性分子。对于非极性分子，混合AA/CG模型得到的结果与完全原子的结果更好地吻合。在50-100 ns的AA/CG模拟过程中，在CG水溶剂化的原子泛素结构和CG脂质双层中的单个原子跨膜α-螺旋和原子机械敏感通道的跨膜部分在很大程度上保持不变，部分原因是分子内相互作用的过度稳定。这项工作突出了一些关键的挑战，对混合AA/CG模型的计算效率和足够准确的生物分子模拟的方式。
Hybrid molecular dynamics simulations of atomistic (AA) solutes embedded in coarse-grained (CG) environment can substantially reduce the computational cost with respect to fully atomistic simulations. However, interfacing both levels of resolution is a major challenge that includes a balanced description of the relevant interactions. This is especially the case for polar solvents such as water, which screen the electrostatic interactions and thus require explicit electrostatic coupling between AA and CG subsystems. Here, we present and critically test computationally efficient hybrid AA/CG models. We combined the Gromos atomistic force field with the MARTINI coarse-grained force field. To enact electrostatic coupling, two recently developed CG water models with explicit electrostatic interactions were used: the polarizable MARTINI water model and the BMW model. The hybrid model was found to be sensitive to the strength of the AA-CG electrostatic coupling, which was adjusted through the relative dielectric permittivity εr(AA-CG). Potentials of mean force (PMFs) between pairs of amino acid side chain analogues in water and partitioning free enthalpies of uncharged amino acid side chain analogues between apolar solvent and water show significant differences between the hybrid simulations and the fully AA or CG simulations, in particular for charged and polar molecules. For apolar molecules, the results obtained with the hybrid AA/CG models are in better agreement with the fully atomistic results. The structures of atomistic ubiquitin solvated in CG water and of a single atomistic transmembrane α-helix and the transmembrane portion of an atomistic mechanosensitive channel in CG lipid bilayers were largely maintained during 50-100 ns of AA/CG simulations, partly due to an overstabilization of intramolecular interactions. This work highlights some key challenges on the way toward hybrid AA/CG models that are both computationally efficient and sufficiently accurate for biomolecular simulations.