THEORY AND MODELING OF IONS IN SOLUTION AND IN ION CHANNELS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们的团队正在利用大规模分子动力学模拟和电子结构计算来研究水和近离子通道蛋白质中离子溶剂化的基本方面。该项目由美国国家科学基金会资助（CHE-0709560水溶液和离子通道中特定离子效应的建模，2007-2010）。该启动提案寻求Teragrid资源，以1）使用AMBER或NAMD代码对水和通道中的离子进行大规模极化分子动力学（MD）模拟2）使用MD模拟中的配置进行MP2级电子结构计算（Gaussian 03）关于涉及离子的簇和更远溶剂分子的外场中的第一壳层溶剂化环境，以及3）在高温下对离子通道蛋白进行大规模MD模拟，以用于潜在的器件应用。在正在进行的研究中，我们已经开发了一种新的形式主义计算溶剂化自由能的准化学理论的基础上。该理论严格地将自由能划分为内壳层、填充层和外壳层/长程贡献。我们已经开发了一个有效的计算策略来处理这三件自由能，并已应用的方法来研究在水中的分子和离子的溶剂化。这项工作使我们对离子溶剂化的驱动力有了新的认识。我们还仔细研究了局部溶剂化结构，并发现一些现有的极化力场高估了由于过度极化的离子的阴离子溶剂化各向异性。在进一步的工作中，我们重新研究了阴离子系统与QM/MM（量子力学/分子力学）的方法，涉及相关电子计算（MP2）嵌入周围的水溶液中的离子/水团簇。这项工作表明，阴离子的极化比以前预测的要少，第一壳层沃茨受它们与其他沃茨的相互作用的影响比受与离子的相互作用的影响大。而且，在离子和附近的沃茨之间可以发生大量的电荷转移。这项工作将对我们对生物物理相互作用的基本理解产生重大影响。在我们的研究中，我们通过经典模拟（AMBER或NAMD）生成了大量的组态，然后用电子结构计算来研究团簇的系综。这些研究需要广泛的MD采样和高斯03 MP2计算的离子/水簇约20个原子的数千种配置。因此，计算需要大量的计算资源。最后一个项目涉及高温下短杆菌肽通道的模拟。这些分子动力学模拟的肽在现实的膜需要模拟数万个原子为ns的时间尺度。我们有兴趣研究这些膜通道在高温（高达100 ° C）下的传输特性，以便在新型燃料电池设备中获得潜在的应用。我们要求为这些初步研究提供全部允许的20万SU，然后提出完整的研究分配建议。5 TB的磁盘或25 TB的磁带存储应该足够了。NAMD、AMBER和Gaussian 03代码将是用于本研究的主要软件，因此我们请求NCSA、SDSC、LONI和IU网站上的资源。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our group is utilizing large-scale molecular dynamics simulations and electronic structure calculations to study the fundamental aspects of ion solvation in water and near ion channel proteins. The project is funded by the National Science Foundation (CHE-0709560 Modeling specific-ion effects in aqueous solutions and ion channels, 2007-2010). This startup proposal seeks Teragrid resources to 1) perform large-scale polarizable molecular dynamics (MD) simulations of ions in water and channels with the AMBER or NAMD codes 2) use configurations from the MD simulations to perform MP2-level electronic structure calculations (Gaussian03) on clusters involving the ions and the first-shell solvation environment in the external field of more distant solvent molecules and 3) perform large-scale MD simulations of ion channel proteins at high temperatures for potential device applications. In ongoing research, we have developed a new formalism for computing solvation free energies based on quasi-chemical theory. That theory rigorously partitions the free energy into inner-shell, packing, and outer-shell/long-ranged contributions. We have developed an efficient computational strategy for handling each of these three pieces of the free energy, and have applied the methodology to studies of the solvation of molecules and ions in water. The work has allowed us to gain new insights into the driving forces for ion solvation. We have also carefully examined the local solvation structure and have found that some existing polarizable force fields over-estimate anion solvation anisotropy due to over-polarization of the ions. In further work, we have re-examined the anion systems with a QM/MM (quantum mechanics/molecular mechanics) approach involving correlated electron calculations (MP2) on ion/water clusters embedded in surrounding water solution. This work has shown that the anions are less polarized than previously predicted, and that the first-shell waters are affected more by their interactions with other waters than by interactions with the ion. Also, substantial charge transfer can occur between the ions and nearby waters. This work should have significant impacts on our basic understanding of biophysical interactions. In our research, we generate a large number of configurations by classical simulation (AMBER or NAMD) and then examine the ensemble of clusters with the electronic structure calculations. The studies require extensive MD sampling and Gaussian03 MP2 calculations on ion/water clusters with roughly 20 atoms for thousands of configurations. The calculations thus require extensive computational resources. The final project concerns simulations of gramicidin channels at high temperatures. These MD simulations of the peptides in realistic membranes require modeling tens of thousands of atoms for ns time scales. We are interested in studying the transport properties of these membrane channels at high temperatures (up to 100o C) for potential applications in novel fuel cell devices. We request the full allowed 200,000 SUs for these initial studies, to be followed by a full Research Allocation proposal. 5 TB of disk, or 25 TB of tape storage should be sufficient. The NAMD, AMBER, and Gaussian03 codes will be the main software used for this research, so we request resources on the NCSA, SDSC, LONI, and IU sites.