Dill Ken A, Ozkan S Banu, Weikl Thomas R, Chodera John D, Voelz Vincent A
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA.
Curr Opin Struct Biol. 2007 Jun;17(3):342-6. doi: 10.1016/j.sbi.2007.06.001. Epub 2007 Jun 14.
The protein folding problem can be viewed as three different problems: defining the thermodynamic folding code; devising a good computational structure prediction algorithm; and answering Levinthal's question regarding the kinetic mechanism of how proteins can fold so quickly. Once regarded as a grand challenge, protein folding has seen much progress in recent years. Folding codes are now being used to successfully design proteins and non-biological foldable polymers; aided by the Critical Assessment of Techniques for Structure Prediction (CASP) competition, protein structure prediction has now become quite good. Even the once-challenging Levinthal puzzle now seems to have an answer--a protein can avoid searching irrelevant conformations and fold quickly by making local independent decisions first, followed by non-local global decisions later.
定义热力学折叠密码;设计一种良好的计算结构预测算法;以及回答莱文索尔关于蛋白质如何能如此快速折叠的动力学机制的问题。蛋白质折叠曾被视为一项重大挑战,近年来已取得了很大进展。折叠密码现在正被成功用于设计蛋白质和非生物可折叠聚合物;在蛋白质结构预测技术关键评估(CASP)竞赛的助力下,蛋白质结构预测如今已相当出色。甚至一度具有挑战性的莱文索尔谜题现在似乎也有了答案——蛋白质可以通过先做出局部独立决策,随后再做出非局部全局决策,从而避免搜索不相关的构象并快速折叠。