The Protein-Folding Problem, 50 Years On

被引:1114
作者
Dill, Ken A. [1 ,2 ,3 ]
MacCallum, Justin L. [1 ]
机构
[1] SUNY Stony Brook, Laufer Ctr Phys & Quantitat Biol, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Dept Phys, Stony Brook, NY 11794 USA
[3] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA
关键词
3-DIMENSIONAL FOURIER SYNTHESIS; X-RAY ANALYSIS; STRUCTURE PREDICTION; NONBIOLOGICAL POLYMER; COMPUTATIONAL DESIGN; DYNAMICS; PATHWAYS; RESOLUTION; FUNNELS; CASP;
D O I
10.1126/science.1219021
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 far more 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.
引用
收藏
页码:1042 / 1046
页数:5
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