Center for Biomolecular NMR, Structure, and Design

该提案要求资金建立一个生物 在state.of.the.art高分辨率NMR和 计算机图形/分子建模方法来确定 生物分子的三维溶液结构和动力学。 的 中心将提供基础设施支持， 一系列需要核磁共振，分子建模， 分子力学/动力学与微扰自由能 计算来设计新的生物分子。 最初，中心 重点将是研究和设计蛋白质，修饰的DNA 类似物和DNA结合药物和蛋白质。 在一些 这些“设计”的生物分子将使用 已建立的合成有机方法或通过自动化DNA或 寡肽合成器。 或者，重组 DNA方法学将用于基因工程 突变蛋白 然后，中心将确定3D结构 设计的生物分子通过2D NMR nd距离几何 方法，并将结构与 计算和建模。 的结构和活动 设计的生物分子将进行比较，以更好地了解 这些生物分子的生物活性。 这个中心将 受益于大量不同的研究人员，估计 大约有120名教职员工。因此，它具有相当大的潜力 以促进独特组合的相互作用， 多学科人才。

This proposal requests funds to establish a Biological Facilities Center in state.of.the.art high.resolution NMR and computer graphics/molecular modeling methodologies to determine the 3D solution structure and dynamics of biomolecules. The Center will provide the infrastructure support for a diverse range ofprojects requiring NMR, molecular modeling, molecular mechanics/dynamics and perturbational free energy calculations to design new biomolecules. Initially the Center's focus will be on the study and design of proteins, modified DNA analogs and DNA binding drugs and proteins. In a number of projects, these "designed" biomolecules will be synthesized using established synthetic organic methods or through automated DNA or oligopeptide synthesizers. Alternatively, recombinant DNA methdologies will be used to genetically engineer mutant proteins. The Center will then determine the 3D structure of the designed biomolecules via 2D NMR nd distance geometry methods and compare the structure with that predicted by the calculations and modeling. Structure and activity of the designed biomoleculeswill be compared to better understand the biological activity of these biomolecules. This center will benefit a large and diverse group of researchers, estimated at about l20 faculty members. Thus, it has considerable potential for fostering interactions of unique combinations of multidisciplinary talent.