STRUCT & FUNCT OF MUTANT VERSIONS OF ALKALINE PHOSPHATASE FROM ESCHERICHIA COLI

我们提出的模拟将有助于阐明这一机制， 离子络合分子作用的能量学和动力学，或 离子受体，在磷脂双层。我们的努力将是 利奥·帕奎特对这些模型离子载体的合成表示赞赏 俄亥俄州立大学研究小组和交通工具测量 与加州大学弗兰克·G·里德尔合作的特征 圣安德鲁斯。我们建议在不同的条件下计算自由能表面 近似级别，最接近也是最 可行。离子与电离层缔合的自由能量学 没有模拟磷脂双层的水溶液。这 应该会给我们提供有关离子溶剂置换的信息 接近电离团，但没有描述不均匀 膜环境。粗略地将膜/溶剂界面模拟为 在两种不相容的流体之间。这仍然缺少许多重要的 特征，但最终界面膜的不均匀性是 那里。令人高兴的是，有实验测量 离子载体介导的两个水溶液区域之间的跨 这种情况所对应的不混溶的非极层。 双分子层内离子载体的真实全原子模拟。我们 希望完成第一阶段和第二阶段的一部分 关于本提案所要求的资源的说明。我们会 研究全原子计算的可行性。

The simulations we proposed will help elucidate the mechanism, energetics and kinetics of the action of ion-complexing molecules, or ionophors, at a phospholipid bilayer. Our efforts will be complimented by synthesis of these model ionophores in Leo Paquette's research group at Ohio State and measurement of transport characteristics in collaboration with Frank G. Ridell at University of St. Andrews. We propose to calculate a free energy surface at various levels of approximation, the most approximation being also the most feasible. Free energetics of ion association with an ionosphore in aqueous solvent with no modeling of a phospholipid bilayer. This should give us information about solvent displacement as the ion approaches the ionophore, but does not describe the inhomogeneous membrane environment. Crudely model the membrane/solvent interface as that between two immiscible fluids. This still lacks many important features, but at last the inhomogeneity of the membrane in terface is there. Happily, there are experimental measurements of ionophore-mediated transport between two aqueous regions across an immiscible non-polar layer to which this situation corresponds. Realistic all-atom simulations of an ionophore within a bilayer. We expect to complete the first and part of the second level of description with the resources requested in this proposal. We will study the feasibility of all-atom calculations.