Optimization of Stuctures and Networks of Proteins

描述(由申请人提供)：这项申请有三个主要目的，利用数学编程工具来解决生物物理激发的问题。第一个目标是提炼从同源关系中获得的蛋白质结构。基于同源性的结构很少具有原子分辨率；这种分辨率对于蛋白质功能的详细建模和药物分子的设计是必要的。基于数学规划方法，设计了一类新的适合于求精问题的能量函数。第二个目标是研究一种新型的网络：蛋白质结构之间的序列流动网络。我们研究由点突变产生的新序列保留在当前折叠中或切换到其他稳定结构(我们排除没有稳定折叠的序列)的过程。对结构的调整是根据稳定性准则来决定的。这是一张网。这项工作定义了一个主方程，它使研究过去(古代)褶皱和充当吸引子的未来结构成为可能。第三个目标是研究蛋白质-蛋白质(物理)相互作用的网络，并将用生物信息学和生物物理方法进行研究。将对序列流网络和蛋白质-蛋白质相互作用网络进行比较，以更好地理解生物机制和识别的进化。与公共健康相关设计预测蛋白质结构和蛋白质相互作用的新算法可能有助于设计新的药物分子。

DESCRIPTION (provided by applicant): This application has three major aims that exploit the use of mathematical programming tools for biophysically motivated problems. The first goal is the refinement of protein structures that are obtained from homology. Structures based on homology are rarely of atomic resolution; a resolution which is necessary for detailed modeling of protein function, and for the design of drug molecules. Based on mathematical programming approach a new class of energy functions, suitable for the refinement problem, will be designed. The second goal is to investigate a new type of network; the network of sequence flow between protein structures. We examine the process in which new sequences, generated by point mutations, remain in the current fold, or switch to other stable structures (we exclude sequences with no stable fold). The adjustments to the structure are accepted or rejected based on stability criterion. The net. work defines a master equation which makes it possible to investigate past (ancient) folds, and future structures that serve as attractors. The third aim examines the network of protein-protein (physical) interactions and will be examined with bioinformatics and biophysical approaches. Comparison will be made between the network of sequence flow and the network of protein-protein interactions to better understand the evolution of biological mechanisms and recognition. PUBLIC HEALTH RELEVANCE The design of new algorithms to predict protein structures and protein-protein interactions is likely to help with the design of new drug molecules.