Silicon Graphics Computer Upgrade

将购买一个硅图形虹膜计算机系统， 计算生物学的研究 有了这个电脑系统， 莱维特教授将带来蛋白质的计算机模拟 分子动力学到足够可靠的程度 和现实的，允许预测的能量，结构和 这些复杂系统的动态特性。 这将是 通过提出具体问题并通过以下方式回答来完成 具体应用的模拟和详细分析， 如下所示： 1. 模拟蛋白质溶液是否足够稳定 以允许对罕见事件进行采样所需的扩展模拟， 准确的平均值？ 牛的扩展模拟 胰蛋白酶抑制剂（BPTI）溶液浓度超过100 皮秒（ps）将证实其方法的进步（使用 所有原子的能量函数，一个灵活的水分子和 光滑截断非键势和严格 坚持节约能源）。 2.蛋白质的溶液结构与 晶体结构？ BPTI扩展弹道分析 计算每个质子间矢量的谱密度 将有可能得到更精确的解 核磁共振实验的结果。 与非弹性中子散射数据的比较也将 进行了 3.简单的能量函数和经典动力学能重现 蛋白质X射线结构的细节 他们将模拟 两个精细的高分辨率蛋白质结构的动力学， BPTI和crambin在它们的天然晶格中。 系统 计算的时间平均结构之间的差异， X射线结构将用于修改能量参数。 4.水是如何渗透和破坏天然蛋白质的 结构在展开的第一阶段？ 哪些交互 首先，极性氢键或非极性货车 der Waals相互作用？ 这种“展开” 波动发生在正常和变性条件下？ 他们 将研究天然BPTI在溶液中的稳定性， 温度、密度（相当于压力）和 二硫键发生了变化。这些方法也将用于 更简单的系统，如α-螺旋和β-发夹 溶液 5. 水分子通过什么途径以什么速率被排出 从蛋白质结合位点 他们将把这些方法应用于 更大的蛋白质，核糖核酸酶和胰蛋白酶/BPTI复合物， 也在实验研究中。

A Silicon Graphics Iris computer system will be acquired for research in computational biology. With this computer system, Professor Levitt will bring computer simulation of protein molecular dynamics to the point where it is sufficiently reliable and realistic to allow prediction of energetic, structural and dynamic properties of these complicated systems. This will be accomplished by asking specific questions and answering them by simulation and detailed analysis of specific applications as follows: 1. Are simulations of proteins in solution sufficiently stable to allow the extended simulation needed to sample rare events and accumulate accurate averages? Extending simulations of bovine pancreatic trypsin inhibitor (BPTI) in solution beyond 100 picoseconds (ps) will confirm their methodological advances (use of all-atom energy functions, a flexible water molecule and a smoothly truncated nonbonded potential together with strict insistence on energy conservation). 2. How does the solution structure of a protein differ from the crystal structure? Analysis of the extended BPTI trajectory by calculating the spectral densities of each inter-proton vector will make it possible to derive a more accurate solution structure from nuclear magnetic resonance experiments. Comparisons to inelastic neutron scattering data will also be made. 3. Can simple energy functions and classical dynamics reproduce the details of protein x-ray structures? They will simulate the dynamics of two well-refined, high-resolution protein structures, BPTI and crambin in their native crystal lattices. Systematic differences between the calculated time-averaged structure and the x-ray structure will be used to modify the energy parameters. 4. How does water penetrate into and disrupt native protein structure in the first stages of unfolding? Which interactions are weakened first, the polar hydrogen bonds or the non-polar van der Waals' interactions? How rapidly do such "unfolding" fluctuations occur under normal and denaturing conditions? They will investigate the stability of native BPTI in solution as temperature, density (equivalent to pressure) and patterns of disulphide bonding are changed. These methods will also be used on simpler systems such as alpha-helices and beta-hairpins in solution. 5. By what path and at what rate are water molecules expelled from protein binding sites? They will apply these methods to larger proteins, ribonuclease and the trypsin/BPTI complex, which are also being studied experimentally.