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

结构体

• 批准号: 6221083
• 负责人: EVAN R KANTROWITZ
• 金额: $ 0.13万
• 依托单位: MELLON PITTS CORPORATION (MPC CORP)
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6221083
• 关键词: biological products; biomedical resource; computers

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.

我们提出的模拟将有助于阐明机制， 离子复合分子的作用的能量和动力学，或 离子型，在磷脂双层。 我们的努力将是 这些模型离子载体在Leo Paquette的合成中称赞 俄亥俄州立大学的研究小组和运输的测量 与大学的弗兰克·G·里德尔合作的特征 圣安德鲁斯。 我们建议在各种 近似级别，最近似值也是最大的 可行的。 离子与电离圈的自由能量 水溶液没有磷脂双层的建模。 这 应该为我们提供有关溶剂位移的信息 接近离子机，但没有描述不均匀的 膜环境。 粗略地将膜/溶剂接口建模为 在两种不混溶的液体之间。 这仍然缺乏许多重要的 功能，但最后，膜中膜的不均匀性是 那里。 令人高兴的是，有实验测量 离子团介导的两个水区域之间的转运 这种情况对应的不可分化的非极性层。 对双层内离子载体的现实全原子模拟。 我们 期望完成第二级的第一和部分 描述本提案中要求的资源。 我们将 研究全原子计算的可行性。