CRYSTALLOGRAPHIC REFINEMENT BY NONLINEAR ESTIMATION

SBIR项目的总体目标是引入一个强大的新的非线性估计框架，用于使用X射线晶体学数据对蛋白质分子的三维结构进行细化。该框架将由ASTER-X（X射线自动结构估计和优化）实现;这是一种新的代码，有望通过提高速度和更大的收敛半径来增加晶体结构的吞吐量。这种增加的通量对于将结构生物学与基因组学和蛋白质组学的爆炸性领域联系起来至关重要。拟议的第一阶段工作的具体目标有两个方面。第一个目标是为早期晶体学模型构建/细化阶段实施一种强大的细化方法，这将减少该过程所需的人工干预和专业知识。我们将评估ASTER-X在收敛半径和速度方面的能力，使用相对简单，可扩展的熔融盒方法来遍历结构;这种方法可以在交互模式下实现。第二个目标是开发一个更先进的ASTER-X版本，允许一次处理整个晶体结构，从而实现相互空间细化。这个高级版本承诺比最先进的细化方法加速一到两个数量级。拟议的商业应用：该SBIR项目的目标是向市场推出一种创新的新软件产品（ASTER-X），用于从X射线晶体学数据确定蛋白质3D结构。ASTER-X通过提高速度和更大的收敛半径来提高晶体结构的吞吐量。ASTER-X将是制药和生物技术行业的研究人员以及学术界的研究人员高度期望的，特别是因为它提供了结构生物学与基因组学和蛋白质组学爆炸领域之间的联系。

The overall goal of this proposed SBIR project is to introduce a powerful new non-linear estimation framework for three-dimensional structure refinement of protein molecules using X-ray crystallographic data. This framework will be enabled by ASTER-X (Automated Structure Estimation and Refinement for X-ray); a new code that promises to increase the throughput of crystallographic structures via improved speed and larger radius of convergence. This increased throughput is essential to link structural biology to the exploding fields of genomics and proteomics. The specific aims of the proposed Phase I work are twofold. The first goal is to implement a powerful refinement method for the early crystallographic model-building/refinement stages that will reduce the amount of human intervention and expertise necessary for this process. We will evaluate the power of ASTER-X in terms of radius of convergence and speed using a relatively straightforward, scalable, molten box approach to traversing the structure; an approach that can be implemented in an interactive mode. The second goal is to develop a more advanced version of ASTER-X that will allow treatment of the entire crystal structure at one time, and will thus enable reciprocal space refinement. This advanced version promises speedups of one to two orders of magnitude over state-of- the-art refinement methods. PROPOSED COMMERCIAL APPLICATIONS: The objective of this SBIR project is to bring to market an innovative new software product (ASTER-X) for protein 3D structure determination from X-ray crystallographic data. ASTER-X offers increased throughput of crystallographic structures via improved speed and larger radius of convergence. ASTER-X will be highly desired by researchers in pharmaceutical and biotechnology industries, as well as by those in academia, especially as it provides a link between structural biology and the exploding fields of genomics and proteomics.