Artifical Intelligence Approach to the Prediction of Three Dimensional Structure of Protein

通过引入久保田的Titan图形工作站和Sun微系统的Sun 3/260，并以此为基础构建一个用于蛋白质结构分析的人工智能系统，我们在本研究项目中获得了以下结果：在预测蛋白质三维结构的问题中，最困难的是只有氨基酸序列信息的情况。经过30年的研究，现在人们普遍认为，基于物理化学原理的方法存在着本质上的困难。因此，在这个项目中，我们尝试了一种基于模式识别的本质上不同的方法，而模式识别又是基于蛋白质的生物进化。为此，我们研究了多肽链片段的主链构象在球状蛋白中的分布。我们发现了一个聚类分布。基于这种分布性质，可以对骨架结构进行定量分类。在预测的问题中，最简单的是预测与位点定向氨基酸取代相关的构象变化。在这种情况下，要求预测变化的精度达到预测函数相关变化所必需的精度。然而，与氨基酸取代相关的构象变化非常小，一般小到甚至小于室温下的波动幅度。这意味着要预测的是动态结构的变化。从这个角度来看，研究方向是动力结构。结果表明，蛋白质动力学具有双重性，即调和类固体方面和非调和类液体方面。

By introducing Kubota's Titan graphic workstation and Sun Micro-system's Sun 3/260 and by constructing therefrom an artificial intelligence system for structural analysis of proteins, we have attained the following results in this research project. Among the problems of predicting 3D structures of proteins, the most difficult is the case where information only of amino acid sequence is available. After 30 years of research is this field it has now been widely believed that the approach based on the physicochemical principle involves essential difficulties. Therefore in this project we have tried an essentially different approach based on the pattern recognition, which in turn is based on the biological evolution of proteins. For this purpose we studied distribution of backbone conformations of fragments of polypeptide chain in the globular proteins. We found a clustered distribution. Based on this property of the distribution a quantitative method of classification of backbone structure is possible.Among the problems of prediction, the easiest is that of predicting conformational changes associated with a site-directed amino acid substitution. In this case it is demanded that the change is predicted to the accuracy necessary to predict associated change of the function. However, conformational change associated with an amino acid substitution is very small, so small in general to be even smaller than the amplitude of fluctuation in the room temperature. This means that what is to be predicted is the change of dynamic structure. From this point of view, studies are directed to the direction of dynamic structures. As a result, it has been elucidated that protein dynamics has dual aspects, harmonic solid-like aspect and anharmonic liquid-like aspect.