蛋白质折叠问题的50年历程要点.docxVIP

The Protein-Folding Problem, 50 Years On 蛋白质折叠问题的50年历程 The protein-folding problem was first posed about one half-century ago. The term refers to three broad questions: (i) What is the physical code by which an amino acid sequence dictates a protein’s native structure? (ii) How can proteins fold so fast? (iii) Can we devise a computer algorithm to predict protein structures from their sequences? We review progress on these problems. In a few cases, computer simulations of the physical forces in chemically detailed models have now achieved the accurate folding of small proteins. We have learned that proteins fold rapidly because random thermal motions cause conformational changes leading energetically downhill toward the native structure, a principle that is captured in funnel-shaped energy landscapes. And thanks in part to the large Protein Data Bank of known structures, predicting protein structures is now farmore successful than was thought possible in the early days. What began as three questions of basic science one half-century ago has now grown into the full-fledged research field of protein physical science. 蛋白质折叠问题是在半个世纪前第一次提出来的。这一术语提到了三大问题:(i) 氨基酸序列决定蛋白质天然结构的物理密码是什么? (2)蛋白质是怎样迅速折叠的?(3) 我们能设计一种计算机算法，让这种算法根据蛋白质的氨基酸序列就能预测蛋白质的结构吗?我们回顾在这些问题上所取得的进展。只在少数情况下, 对于精细的化学模型中的物理外力，计算机模拟能够实现小型蛋白的正确折叠。我们了解到蛋白质迅速折叠是因为随机热运动使得构象发生改变，而根据漏斗状的能量图景（funnel-shaped energy landscapes）中所体现的原理，构象变化会使蛋白质沿着下坡路回归到天然结构。还得感谢蛋白质数据库（PDB）中的已知结构,现在预测蛋白质结构远比早期预想的要成功。半个世纪前，以这三个问题开始的基础科学现如今已经发展为一个对蛋白质自然科学进行研究的的成熟领域。 Protein molecules embody a remarkable relationship between structure and function at the molecular level. Proteins perform many different functions in biochemistry. A protein’s biological mechanism is determined by its three-dimensional (3D) native structure, which in turn is encoded in its 1D string of amino acid monomers. 蛋白质分子在分子水平上具体体现了蛋白质结构和其功能之间的显著关系。蛋白质白质在生物化学中有许多不同的功能。蛋白质的三维(3 D)天然结构决定它的生物学机制，而反过来，蛋白质的氨基酸单体的一维链又对它的天然机构进行编码。 This year marks the 50th anniversary of the 1962 Nobel