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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们小组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。该项目由国家科学基金会资助(CHE-0709560水溶液和离子通道中的特定离子效应建模，2007年至2010年)。这项启动计划寻求TeraGrid资源1)执行大规模的可极化分子动力学(MD)模拟水中的离子和具有AMBER或NAMD代码的通道2)使用MD模拟中的配置来执行MP2级别的电子结构计算(Gaussian03)涉及离子和更远的溶剂分子外场中的第一壳层溶剂化环境的团簇，3)为了潜在的设备应用，在高温下执行大规模的离子通道蛋白质的MD模拟。在正在进行的研究中，我们发展了一种新的基于准化学理论的计算溶剂化自由能的形式。该理论严格地将自由能划分为内壳层、堆积和外壳层/长程贡献。我们开发了一种有效的计算策略来处理这三个自由能中的每一个，并将该方法应用于分子和离子在水中的溶剂化研究。这项工作使我们对离子溶剂化的驱动力有了新的见解。我们还仔细研究了局部溶剂化结构，发现由于离子的超极化，一些现有的可极化力场高估了阴离子溶剂化的各向异性。在进一步的工作中，我们用QM/MM(量子力学/分子力学)方法重新研究了阴离子体系，该方法涉及嵌入在周围水溶液中的离子/水团簇的关联电子计算(MP2)。这项工作表明，阴离子的极化程度比之前预测的要低，第一层水更多地受到它们与其他水的相互作用的影响，而不是与离子的相互作用。此外，离子和附近水域之间可能发生大量的电荷转移。这项工作应该会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)产生了大量的组态，然后用电子结构计算考察了团簇的系综。这项研究需要大量的MD采样和Gaussian03MP2计算，计算的离子/水团簇大约有20个原子，有数千种构型。因此，计算需要大量的计算资源。最后一个项目涉及高温下的格雷西丁通道的模拟。在真实的膜中对多肽进行分子动力学模拟需要对数万个原子进行纳秒时间尺度的建模。我们有兴趣研究这些膜通道在高温(高达100摄氏度)下的传输特性，以期在新型燃料电池器件中得到潜在的应用。我们要求为这些初步研究提供全部允许的200,000个SU，然后是一个完整的研究分配方案。5 TB的磁盘或25 TB的磁带存储应该足够了。NAMD、AMBER和Gaussian03代码将是本研究使用的主要软件，因此我们在NCSA、SDSC、LONI和IU站点上请求资源。

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.