Srinivasan R, Rose G D
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Proteins. 1995 Jun;22(2):81-99. doi: 10.1002/prot.340220202.
We describe LINUS, a hierarchic procedure to predict the fold of a protein from its amino acid sequence alone. The algorithm, which has been implemented in a computer program, was applied to large, overlapping fragments from a diverse test set of 7 X-ray-elucidated proteins, with encouraging results. For all proteins but one, the overall fragment topology is well predicted, including both secondary and supersecondary structure. The algorithm was also applied to a molecule of unknown conformation, groES, in which X-ray structure determination is presently ongoing. LINUS is an acronym for Local Independently Nucleated Units of Structure. The procedure ascends the folding hierarchy in discrete stages, with concomitant accretion of structure at each step. The chain is represented by simplified geometry and folds under the influence of a primitive energy function. The only accurately described energetic quantity in this work is hard sphere repulsion--the principal force involved in organizing protein conformation [Richards, F. M. Ann. Rev. Biophys. Bioeng. 6:151-176, 1977]. Among other applications, the method is a natural tool for use in the human genome initiative.
我们描述了LINUS，这是一种仅根据蛋白质氨基酸序列预测其折叠结构的分层程序。该算法已在计算机程序中实现，并应用于来自7种经X射线解析的蛋白质的不同测试集的大型重叠片段，结果令人鼓舞。对于除一种蛋白质外的所有蛋白质，整体片段拓扑结构都能得到很好的预测，包括二级结构和超二级结构。该算法还应用于构象未知的分子groES，目前正在对其进行X射线结构测定。LINUS是局部独立成核结构单元（Local Independently Nucleated Units of Structure）的首字母缩写。该程序在离散阶段逐步提升折叠层次，每一步都伴随着结构的增加。该链由简化的几何形状表示，并在原始能量函数的影响下折叠。这项工作中唯一准确描述的能量量是硬球排斥力——这是参与构建蛋白质构象的主要力量[理查兹，F.M.《生物物理与生物工程年度评论》6:151 - 176，1977]。在其他应用中，该方法是人类基因组计划中一种很自然的工具。
