NMR STRUCTURE REFINEMENT BY NONLINEAR ESTIMATION

该SBIR项目的长期目标是将其推向市场 一个 创新的蛋白质三维(3D)软件 结构 从核磁共振数据中进行测定和提纯。这一新代码名为 紫玛瑙 (自动结构估计和细化)，实现了一种 从根本上说 生物分子三维结构研究的新范式提供了 不仅提供显著的加速(高达三个数量级 大小) 在传统方法之上，而且还提供了 治疗 所有已知的统计模型和测量不确定度 (包括 不确定的质子共振分配)。又快又准 蛋白质三维结构的确定具有重要意义 为 药物设计。 第二阶段的具体目标是开发一种商业 的原型 艾斯特。这将分两个阶段实现。第一阶段将 结果 在完全的精细化能力和涉及：完整的 成立为法团 所有可用的化学信息(例如，力场 参数)； 开发更复杂的内存管理技术以 方法所需的大型(但稀疏)矩阵 研究方法： 以及与现有代码的互操作性的开发。这个 第二 Stage完成无缝确定/细化功能 通过开发和实施先进技术 至 扩大方法论的收敛半径。

The long-term objective of this SBIR project is to bring to market an innovative new software for protein three-dimensional (3D) structure determination and refinement from NMR data. This new code, named ASTER (Automated STructure Estimation and Refinement), realizes a fundamentally new paradigm for biomolecular 3D structure research that offers to provide not only significant speedups (up to three orders of magnitude) over conventional methodologies, but also a framework for the treatment of all known statistical model and measurement uncertainties (including uncertain proton resonance assignments). The fast and accurate determination of protein 3D structures has significant implications for drug design. The specific goal of the Phase II is to develop a commercial prototype of ASTER. This will be achieved in two stages. The first stage will result in complete refinement capabilities and involves: the full incorporation of all available chemical information (e.g., force field parameters); the development of more sophisticated memory management techniques to accommodate the large (but sparse) matrices required by the methodology: and, the development of interoperability with existing codes. The second stage completes the seamless determination/refinement functionality through the development and implementation of advanced techniques to expand the radius of convergence of the methodology.