Center for Biomolecular NMR, Structure, and Design

该提案要求提供资金，在加州建立一个生物设施中心。高分辨率核磁共振和计算机图形学/分子建模方法，以确定生物分子的3D溶液结构和动力学。该中心将为各种项目提供基础设施支持，这些项目需要核磁共振、分子建模、分子力学/动力学和微扰自由能计算来设计新的生物分子。该中心最初的重点将是研究和设计蛋白质、修饰的DNA类似物以及DNA结合药物和蛋白质。在许多项目中，这些“设计”的生物分子将使用现有的合成有机方法或通过自动DNA或寡肽合成器来合成。或者，重组DNA方法学将被用于对突变蛋白质进行基因工程。然后，中心将通过2D核磁共振和距离几何方法确定所设计的生物分子的三维结构，并将其结构与计算和建模预测的结构进行比较。将对设计的生物分子的结构和活性进行比较，以更好地了解这些生物分子的生物活性。该中心将使一大批不同的研究人员受益，估计约有120名教职员工。因此，它在培养多学科人才的独特组合方面具有相当大的潜力。

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.