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

我们提出的模拟将有助于阐明机制， 离子络合分子作用的能量学和动力学，或 离子载体，在磷脂双层。 我们的努力将是 在Leo Paquette的研究中，这些模型离子载体的合成得到了补充 俄亥俄州研究小组和运输测量 与Frank G.里德尔大学 圣安德鲁斯 我们建议计算一个自由能表面在不同的 近似水平，最近似也是最 可行 离子与离子交换剂缔合的自由能 水性溶剂，没有磷脂双层的建模。 这 应该给我们关于溶剂置换的信息， 接近离子载体，但没有描述不均匀的 膜环境 将膜/溶剂界面粗略建模为 在两种不混溶的流体之间。 这仍然缺乏许多重要的 特征，但最后膜界面的不均匀性是 那里 令人高兴的是，有实验测量， 离子载体介导的跨膜两个水区域之间的转运 不混溶的非极性层，这种情况对应于该层。 双层膜内离子载体的真实全原子模拟。 我们 预计将完成第一和第二水平的一部分， 说明与本提案所要求的资源相符。 我们将 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.