Atomistic biosimulations

某些天然和人工合成的小阳离子肽具有杀死细菌的能力。其中一些多肽也不会攻击哺乳动物细胞，因此是传统抗生素的潜在替代品，这是非常可取的，因为细菌对传统抗生素产生了耐药性。长期目标是在分子水平上理解，使用原子计算机模拟方法，这些抗菌肽如何杀死细菌的机制，通常通过与细胞质膜的相互作用，以及它们如何区分细菌和哺乳动物细胞膜。在这一领域提出了三个项目。第一个测试将测试Tom Gill教授（Dalhousie）的假设，即天然肽鱼精蛋白通过膜蛋白OmpF穿过大肠杆菌外膜。我们将模拟鱼精蛋白在孔内的局部自由能和局部扩散系数，以确定鱼精蛋白是否可以通过。第二个项目是发现由Bob Hancock教授（UBC）设计的两个新的非常小的合成肽的非凡致命性的分子基础。我们正在模拟肽的结合自由能来模拟细菌样膜，也模拟哺乳动物样膜，以确定肽的选择性特性。第三个项目是通过模拟研究新的汉考克肽的聚集特性，以验证这些肽首先以大约6个为一组聚集在一起，然后在细菌膜上形成桶状的开放孔，从而导致细菌细胞死亡的假设。

Certain natural and synthetic small cationic peptides have the ability to kill bacteria. Some of these peptides do not also attack mammalian cells, and are therefore potential replacements for traditional antibiotics, which is very desirable because of the development of antibiotic resistance of bacteria to traditional antibiotics. A long term goal is to understand at the molecular level, using atomistic computer simulation methods, the mechanisms of how these antimicrobial peptides kill bacteria, often through interaction with the cytoplasmic membrane, and how some of them can discriminate between bacterial and mammalian cell membranes. Three projects in this area are proposed. The first will test test the hypothesis of Prof. Tom Gill (Dalhousie) that the natural peptide protamine crosses the E.coli outer membrane via the membrane protein OmpF. We will simulate the local free energy and local diffusion coefficient for protamine inside the pore of OmpF to determine if protamine can pass through. A second project is to discover the molecular basis for the extraordinary lethality of two new very small synthetic peptides designed by Prof. Bob Hancock (UBC). We are simulating the binding free energies of the peptides to model bacterial-like membranes, and also to model mammalian-like membranes, to determine the selectivity properties of the peptides. The third project is to study by simulation the aggregation properties of the new Hancock peptides to test the hypothesis that these peptides first aggregate in groups of about six and then form barrel-like open pores in the bacterial membrane, which leads to bacterial cell death.