Department of Mathematics, The University of Western Ontario, 1151 Richmond Street, London, ON N6A 5B7, Canada.
Centre for Advanced Materials and Biomaterials Research, The University of Western Ontario, 1151 Richmond Street, London, ON N6A 5B7, Canada.
Int J Mol Sci. 2022 Apr 21;23(9):4591. doi: 10.3390/ijms23094591.
The development of AlphaFold2 marked a paradigm-shift in the structural biology community. Herein, we assess the ability of AlphaFold2 to predict disordered regions against traditional sequence-based disorder predictors. We find that AlphaFold2 performs well at discriminating disordered regions, but also note that the disorder predictor one constructs from an AlphaFold2 structure determines accuracy. In particular, a naïve, but non-trivial assumption that residues assigned to helices, strands, and H-bond stabilized turns are likely ordered and all other residues are disordered results in a dramatic overestimation in disorder; conversely, the predicted local distance difference test (pLDDT) provides an excellent measure of residue-wise disorder. Furthermore, by employing molecular dynamics (MD) simulations, we note an interesting relationship between the pLDDT and secondary structure, that may explain our observations and suggests a broader application of the pLDDT for characterizing the local dynamics of intrinsically disordered proteins and regions (IDPs/IDRs).
AlphaFold2 的发展标志着结构生物学领域的范式转变。在此，我们评估了 AlphaFold2 预测无规则区域的能力，以对抗传统基于序列的无规则预测器。我们发现 AlphaFold2 在区分无规则区域方面表现良好，但也注意到从 AlphaFold2 结构构建的无规则预测器决定了准确性。特别是，一个天真但并非微不足道的假设，即分配给螺旋、链和氢键稳定的转角的残基可能是有序的，而所有其他残基都是无序的，这导致了无序的显著高估；相反，预测的局部距离差异测试 (pLDDT) 提供了残基无序的极好衡量标准。此外，通过使用分子动力学 (MD) 模拟，我们注意到 pLDDT 与二级结构之间存在有趣的关系，这可能解释了我们的观察结果，并表明 pLDDT 更广泛地应用于表征固有无序蛋白质和区域 (IDPs/IDRs) 的局部动力学。
