PROTEIN DYNAMICS AND NMR--SOLUTION STRUCTURE

有了这笔赠款，我们计划继续我们在蛋白质领域的工作。 核磁共振法测定其结构。我们最近报道了 构建一种新的计算机程序，Protean，它同时 决定分子结构以及位置的不确定性 分子内的每个原子。我们还报道了另外一个节目， Bloch，它计算了核磁共振核的预期建立曲线 Overhauser增强(NOE)测量。 我们建议建立两个新的计算机程序，这将使我们能够 研究蛋白质在溶液中的动力学，以期获得更多 准确预测与观测光谱相匹配的结构。 第一个程序Bloch*将允许预测 一种不确定蛋白质结构的核磁共振NOE测量。这部小说 该计划的一个方面是，它将使用对 分子内原子的不确定性不仅可以预测光谱 预期来自刚性分子，但也包括一个分子的光谱 在每个原子的位置上都有微分不确定。这将是 使我们能够预测更准确的光谱，考虑到 分子内位置不确定性的影响。第二个程序， Protean*，将产生蛋白质动态运动模型，解释 观察到的核磁共振谱。这些模型将来自三个来源： 已知的分子化学结构，原子中的不确定性 由我们的结构确定程序计算的位置，以及 分子运动在哪里以及如何发生的简单模拟 大分子。

With this grant we propose to continue our work in the domain of protein structure determination by NMR. We have recently reported the construction of a novel computer program, PROTEAN, which simultaneously determines molecular structure as well as the uncertainty in the position of each atom within the molecule. We have also reported another program, BLOCH, which calculates the expected build-up curve for NMR Nuclear Overhauser Enhancement (NOE) measurements. We propose to build two new computer programs which will allow us to investigate the dynamics of proteins in solution with a view to more accurately predicting structures that will match the observed spectra. The first program, BLOCH*, will allow the prediction of the build-up of NMR NOE measurements from an uncertain protein structure. The novel aspect of this program is that it will use explicit estimates of the uncertainty of atoms within the molecule to predict not only the spectra expected from a rigid molecule, but also the spectra of a molecule which has differential uncertainty in the position of each atom. This will allow us to predict more accurate spectra that take into account the effects of positional uncertainty within a molecule. The second program, PROTEAN*, will produce models of protein dynamic motion which explain the observed NMR spectra. These models will be derived from three sources: the known chemical structure of the molecule, the uncertainty in atomic positions as calculated by our structure determination program, and simple simulations of where and how molecular motion can take place in a large molecule.