Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA.
Proteins. 2009 Nov 15;77(3):670-84. doi: 10.1002/prot.22481.
The ability to predict the absolute stability of proteins based on their corresponding sequence and structure is a problem of great fundamental and practical importance. In this work, we report an extensive, refinement and validation of our recent approach (Roca et al., FEBS Lett 2007;581:2065-2071) for predicting absolute values of protein stability DeltaG(fold). This approach employs the semimacroscopic protein dipole Langevin dipole method in its linear response approximation version (PDLD/S-LRA) while using the best fitted values of the dielectric constants epsilon'(p) and epsilon'(eff) for the self energy and charge-charge interactions, respectively. The method is validated on a diverse set of 45 proteins. It is found that the best fitted values of both dielectric constants are around 40. However, the self energy of internal residues and the charge-charge interactions of Lys have to be treated with care, using a somewhat lower values of epsilon'(p) and epsilon'(eff). The predictions of DeltaG(fold) reported here, have an average error of only 1.8 kcal/mole compared to the observed values, making our method very promising for estimating protein stability. It also provides valuable insight into the complex electrostatic phenomena taking place in folded proteins.
基于蛋白质序列和结构预测其绝对稳定性的能力是一个具有重要基础和实际意义的问题。在这项工作中，我们对最近的方法（Roca 等人，FEBS Lett 2007；581:2065-2071）进行了广泛的改进和验证，用于预测蛋白质稳定性变化（DeltaG(fold)）的绝对值。该方法在其线性响应近似版本（PDLD/S-LRA）中采用半宏观蛋白质偶极 Langevin 偶极子方法，同时分别使用自能和电荷-电荷相互作用的最佳拟合介电常数 epsilon'(p) 和 epsilon'(eff)。该方法在一组 45 种不同的蛋白质上进行了验证。结果发现，两种介电常数的最佳拟合值都在 40 左右。然而，内部残基的自能和 Lys 的电荷-电荷相互作用需要小心处理，使用略低的 epsilon'(p) 和 epsilon'(eff) 值。与观察值相比，这里报告的 DeltaG(fold)预测值的平均误差仅为 1.8 kcal/mol，这使得我们的方法非常有前途，可以用于估计蛋白质的稳定性。它还提供了对折叠蛋白质中发生的复杂静电现象的有价值的见解。
