Jones D, Thornton J
Department of Biochemistry and Molecular Biology, University College, London, U.K.
J Comput Aided Mol Des. 1993 Aug;7(4):439-56. doi: 10.1007/BF02337560.
An important, yet seemingly unattainable, goal in structural molecular biology is to be able to predict the native three-dimensional structure of a protein entirely from its amino acid sequence. Prediction methods based on rigorous energy calculations have not yet been successful, and best results have been obtained from homology modelling and statistical secondary structure prediction. Homology modelling is limited to cases where significant sequence similarity is shared between a protein of known structure and the unknown. Secondary structure prediction methods are not only unreliable, but also do not offer any obvious route to the full tertiary structure. Recently, methods have been developed whereby entire protein folds are recognized from sequence, even where little or no sequence similarity is shared between the proteins under consideration. In this paper we review the current methods, including our own, and in particular offer a historical background to their development. In addition, we also discuss the future of these methods and outline the developments under investigation in our laboratory.
结构分子生物学中一个重要却似乎难以实现的目标是能够完全根据蛋白质的氨基酸序列预测其天然三维结构。基于严格能量计算的预测方法尚未成功，目前最佳结果来自同源建模和统计二级结构预测。同源建模仅限于已知结构的蛋白质与未知蛋白质之间存在显著序列相似性的情况。二级结构预测方法不仅不可靠，而且也没有提供通向完整三级结构的明显途径。最近，已开发出一些方法，通过这些方法可以从序列中识别出完整的蛋白质折叠，即使所考虑的蛋白质之间几乎没有或没有序列相似性。在本文中，我们回顾了当前的方法，包括我们自己的方法，尤其提供了这些方法发展的历史背景。此外，我们还讨论了这些方法的未来，并概述了我们实验室正在研究的进展情况。
