Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts.
Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts.
Biophys J. 2020 Jun 16;118(12):2872-2878. doi: 10.1016/j.bpj.2020.04.027. Epub 2020 May 1.
The distribution of protein stability effects is known to be well approximated by a Gaussian distribution from previous empirical fits. Starting from first-principles statistical mechanics, we more rigorously motivate this empirical observation by deriving per-residue-position protein stability effects to be Gaussian. Our derivation requires the number of amino acids to be large, which is satisfied by the standard set of 20 amino acids found in nature. No assumption is needed on the number of residues in close proximity in space, in contrast to previous applications of the central limit theorem to protein energetics. We support our derivation results with computational and experimental data on mutant protein stabilities across all types of protein residues.
蛋白质稳定性效应的分布，根据以往的经验拟合，已知很好地近似于正态分布。从第一性原理统计力学出发，我们通过推导出每个残基位置的蛋白质稳定性效应是正态分布的，更严格地证明了这一经验观察。我们的推导需要氨基酸数量很大，这在自然界中发现的标准 20 种氨基酸中得到满足。与之前将中心极限定理应用于蛋白质能量学的情况不同，我们不需要对空间上接近的残基数量做出假设。我们通过对所有类型的蛋白质残基的突变体蛋白质稳定性的计算和实验数据来支持我们的推导结果。
