Hills Ronald D, Brooks Charles L
Department of Molecular Biology and Kellogg School of Science and Technology, Scripps Research Institute, La Jolla, California, USA.
Biophys J. 2008 Nov 1;95(9):L57-9. doi: 10.1529/biophysj.108.143388. Epub 2008 Aug 15.
The relationship between the folding landscape and function of evolved proteins is explored by comparison of the folding mechanisms for members of the flavodoxin fold. CheY, Spo0F, and NtrC have unrelated functions and low sequence homology but share an identical topology. Recent coarse-grained simulations show that their folding landscapes are uniquely tuned to properly suit their respective biological functions. Enhanced packing in Spo0F and its limited conformational dynamics compared to CheY or NtrC lead to frustration in its folding landscape. Simulation as well as experimental results correlate with the local density of native contacts for these and a sample of other proteins. In particular, protein regions of low contact density are observed to become structured late in folding; concomitantly, these dynamic regions are often involved in binding or conformational rearrangements of functional importance. These observations help to explain the widespread success of Gō-like coarse-grained models in reproducing protein dynamics.
通过比较黄素氧还蛋白折叠家族成员的折叠机制，研究了进化蛋白质的折叠态势与功能之间的关系。CheY、Spo0F和NtrC具有不相关的功能且序列同源性较低，但具有相同的拓扑结构。最近的粗粒度模拟表明，它们的折叠态势经过独特调整，以恰当地适应各自的生物学功能。与CheY或NtrC相比，Spo0F中增强的堆积及其有限的构象动力学导致其折叠态势出现挫折。模拟以及实验结果与这些蛋白质和其他蛋白质样本的天然接触局部密度相关。特别是，观察到低接触密度的蛋白质区域在折叠后期才形成结构；与此同时，这些动态区域通常参与具有功能重要性的结合或构象重排。这些观察结果有助于解释类Gō粗粒度模型在再现蛋白质动力学方面广泛成功的原因。
