Structure, Disorder and Dynamics in Crambin Crystals at Resolution

这项提案的目标是获得一种蛋白质的图片， 它的溶剂在原子分辨率，并测试如何以及平均 结构中原子的位置和迁移率由下式建模： 分子动力学计算 可以实现这一点 通过实验确定蛋白质的振动， 平衡结构，并从理论上 通过使用经验力场。 Crambin是一种独特的疏水性植物蛋白（MW = 4720）， 因为它的衍射超过0.83 A并且具有99%的衍射 在此分辨率限度下观察到的数据。 这意味着它的结构 可以不受蛋白质的通常限制而测定 精致。 虽然crambin的功能还不清楚，但它已经 作为局部麻醉剂的活性。 上述目标将通过以下方式使用crambin来实现： 具体手段：对crambin模型进行无限制的改进 与0.83 A，130 K和0.945 A，300 K的X射线数据进行比较; 在300 K时中子和X射线数据的共同精化; 多温X射线数据压缩;全晶体分子 动力学模拟和与X射线结构的比较;以及 蛋白质水结构预测方法的分析。 %%% 该项目提供了一个独特的机会，以获得 蛋白质分子的实验图片，它的周围 溶剂，及其动态运动在极其尖锐的细节，使用 单晶X射线衍射。 这些优良的特性 所揭示的可以与目前正在被 用来预测和改进蛋白质的结构。 的事实 蟹爪兰的晶体非常有序， 这些细节的确定和测试。

The goal of this proposal is to obtain a picture of a protein and its solvent at atomic resolution and to test how well the average position and mobility of atoms in the structure are modeled by molecular dynamics calculations. This can be accomplished experimentally by determining the protein's vibration and equilibrium structure using diffraction methods and theoretically by using empirical force fields. Crambin is a hydrophobic, plant protein (MW = 4720) that is unique because it diffracts beyond 0.83 A and has 99% of its diffraction data observed at this resolution limit. This means its structure can be determined free of the usual restraints of protein refinement. Although crambin's function is not yet known, it has activity as a local anesthetic. The above goal will be addressed using crambin by the following specific means: unrestrained refinement of the crambin model against the 0.83 A, 130 K and the 0.945 A, 300 K X-ray data; corefinement of neutron and X-ray data at 300 K; refinement of crambin X-ray data at multiple temperatures; full-crystal molecular dynamics simulations and comparison with the X-ray structure; and analysis of the methods to predict protein water structure. %%% This project provides a unique opportunity to obtain an experimental picture of a protein molecule, its surrounding solvent, and its dynamic movement in extremely sharp detail using single crystal X-ray diffraction. The fine features that are revealed can be tested against theories that are currently being used to predict and refine the architecture of proteins. The fact that crystals of crambin are extremely well ordered make possible the determination and testing of these details.