Geierhaas Christian D, Salvatella Xavier, Clarke Jane, Vendruscolo Michele
MRC Centre for Protein Engineering, University of Cambridge, Cambridge CB2 1EW, UK.
Protein Eng Des Sel. 2008 Mar;21(3):215-22. doi: 10.1093/protein/gzm092.
It has been suggested that Phi-values, which allow structural information about transition states (TSs) for protein folding to be obtained, are most reliably interpreted when divided into three classes (high, medium and low). High Phi-values indicate almost completely folded regions in the TS, intermediate Phi-values regions with a detectable amount of structure and low Phi-values indicate mostly unstructured regions. To explore the extent to which this classification can be used to characterise in detail the structure of TSs for protein folding, we used Phi-values divided into these classes as restraints in molecular dynamics simulations. This type of procedure is related to that used in NMR spectroscopy to define the structure of native proteins from the measurement of inter-proton distances derived from nuclear Overhauser effects. We illustrate this approach by determining the TS ensembles of five proteins and by showing that the results are similar to those obtained by using as restraints the actual numerical Phi-values measured experimentally. Our results indicate that the simultaneous consideration of a set of low-resolution Phi-values can provide sufficient information for characterising the architecture of a TS for folding of a protein.
有人提出，Phi值可用于获取蛋白质折叠过渡态（TSs）的结构信息，将其分为三类（高、中、低）时，能得到最可靠的解释。高Phi值表明TS中几乎完全折叠的区域，中等Phi值表明有可检测到的结构量的区域，低Phi值表明大多为无结构的区域。为了探究这种分类在多大程度上可用于详细表征蛋白质折叠TS的结构，我们在分子动力学模拟中使用分为这些类别的Phi值作为约束条件。这种程序与核磁共振光谱中用于根据核Overhauser效应测量得到的质子间距离来确定天然蛋白质结构的程序相关。我们通过确定五种蛋白质的TS集合，并表明结果与通过使用实验测量的实际数值Phi值作为约束条件获得的结果相似，来说明这种方法。我们的结果表明，同时考虑一组低分辨率的Phi值可为表征蛋白质折叠TS的结构提供足够的信息。
