INTERACTIONS OF ANESTHETICS WITH WATER-LIPID INTERFACES

这个项目的目标是定义麻醉剂化合物如何 兴趣与脂膜相互作用，并与浓度相关 这些化合物在水-膜界面上的结构上 相似的化合物，从强效麻醉剂到非麻醉剂 麻醉剂，将被确定为检验麻醉剂的假设 只有当麻醉剂在界面上的浓度达到一定程度时，才会产生效果 就足够了。这一假说是由艾格最近的发现提出的。 单凭亲脂性还不足以预测 吸入麻醉剂。还要求具有最低程度的亲水性 来制造麻醉剂。 在拟议计算的第一阶段，势能 分子动力学计算中所需的函数将被设计并 通过比较所选化合物在 水和正己烷与测量的溶解度。然后，转移到 这些化合物跨越日益复杂的界面(水-己烷， 水-糖脂、水-磷脂)将被模拟。的约束性 对界面的麻醉剂将根据微扰进行分析 在由这些物质产生的膜和界面水的结构中 化合物。 对麻醉剂相互作用分子基础的认识 与具有水-膜界面的非麻醉剂化合物相比 提高我们对麻醉作用部位和机制的认识。 麻醉剂与理化性质之间的相关性得到改善 从拟议的计算中得出的麻醉剂化合物 将有助于设计更好的麻醉药的未来效果。

The objective of this project are to define how compounds of anesthetic interest interact with lipid membranes and to correlate the concentration of these compounds at the water-membranes interface with structurally similar compounds, each ranging from potent anesthetics to non anesthetics, will be determined to test the hypothesis that an anesthetic effect occurs only when the concentration of anesthetic at the interface is sufficient. This hypothesis is motivated by recent findings by Eger that lipophilicity alone is not sufficient to predict the potency of inhaled anesthetics. A minimum level of hydrophilicity is also required to produce anesthesia. In the first stage of the proposed calculations, the potential energy functions needed in molecular dynamics calculations, will be designed and tested by comparing calculated solubilities of the selected compounds in water and hexane with the measured solubilities. Then, the transfer of these compounds across interfaces of increasing complexity (water-hexane, water-glycolipid, water-phospholipid) will be simulated. The binding of anesthetics to the interface will be analyzed in terms of perturbations in the structure of membranes and interfacial water created by these compounds. An understanding of the molecular basis for interactions of anesthetic vs. non anesthetic compounds with the water-membrane interface will advance our knowledge of the site and mechanism of anesthetic action. Improved correlation between anesthetic and physical-chemical properties of anesthetic compounds that should result from the proposed calculations will be helpful in future effects to design better anesthetics.