COMPUTER MODELING AND OTHER THEORETICAL STUDIES

研究开始在两个领域的膜模拟。在第一，“水线”在脂质双层的稳定性进行了研究，通过进行一系列的分子动力学（MD）模拟开始与完整的（模型构建）线穿越双层。 通过氢键保持在一起的线显示出在膜内部的高度疏水环境中相对稳定;即，单个配置在接近100 ps的时间内保持完整。 这一结果支持了水介导的质子跨膜传导的模型。模拟也进行了水/辛烷/水“三明治”的水线。水线的衰变与脂质双层的衰变有质的差异，突出了这种流行的膜模型系统的局限性。提出了一种在P21周期边界条件下模拟脂双层膜的方法。 在这些边界条件下，脂质在离开初级模拟室时穿过对侧小叶。 这使得膜能够根据结合肽时预期的表面积变化进行调整，并且代表了我们模拟复杂膜的能力的重大进步。 纯辛基葡糖苷（OG）胶束和OG/肽复合物的模拟继续进行。 最显著的结果是，在4 ns的模拟过程中，27种脂质的溶液聚集成胶束。 这表明，各种各样的系统和行为，最终可以研究与MD模拟。

Research was begun in two areas of membrane simulations. In the first, the stability of "water wires" in the lipid bilayer was investigated by carrying out a series of molecular dynamics (MD) simulations starting with an intact (model built) wire traversing the bilayer. The wires, which are held together by hydrogen bonds were shown to be relatively stable in the highly hydrophobic environment of the membrane interior; i.e., individual configurations remained intact for close to 100 ps. This result supports a model of water mediated proton conduction across membranes. Simulations were also carried out on water wires in a water/octane/water "sandwich". The decay of the water wires showed qualitative differences with the decay in the lipid bilayer, highlighting the limitations in this popular membrane model system. A method for simulating lipid bilayers in P21 periodic boundary conditions was developed. With these boundary conditions a lipid traverses to the opposite leaflet when leaving the primary simulation cell. This allows the membrane to adjust to changes in surface area as would be expected when binding a peptide, and represents a signficant advance in our ability to simulate complex membranes. Simulations of pure octyl glucoside (OG) micelles and OG/peptide complexes continued. The most significant result was that a solution of 27 lipids aggregated into a micelle during a 4 ns simulation. This indicates that a wide variety of systems and behavior can finally be studied with MD simulation.