Department of Chemistry , University of Basel , Klingelbergstrasse 80 , 4056 Basel , Switzerland.
Department of Chemistry , Brown University , Providence , Rhode Island 02912 , United States.
J Phys Chem B. 2019 Mar 7;123(9):1961-1972. doi: 10.1021/acs.jpcb.8b11454. Epub 2019 Feb 21.
The effect of single amino acid mutations on the rebinding dynamics of nitrogen monoxide (NO) to myoglobin is investigated using reactive molecular dynamics simulations. In particular, mutations of residues surrounding the heme-active site (Leu29, His64, Val68) were considered. Consistent with experiments, all mutations studied here have a significant effect on the kinetics of the NO-rebinding process, which consists of a rapid (several 10 ps) and a slow (100s of ps) time scale. For all modifications considered, the time scales and rebinding fractions agree to within a few percents with results from experiments by adjusting one single, physically meaningful, conformationally averaged quantity: the asymptotic energy separation between the NO-bound (A) and photodissociated (A) states. It is furthermore shown that the thermodynamic stability of wild-type versus mutant Mb for the ligand-free and ligand-bound variants of the protein can be described by the same computational model. Therefore, ligand kinetics and thermodynamics are related in a direct fashion akin to Φ-value analysis, which establishes a relationship between protein folding rates and thermal stability of proteins.
使用反应分子动力学模拟研究了单个氨基酸突变对肌红蛋白与一氧化氮（NO）重新结合动力学的影响。特别考虑了围绕血红素活性位点（Leu29、His64、Val68）的残基突变。与实验一致，这里研究的所有突变都对 NO 再结合过程的动力学有显著影响，该过程由快速（几个 10 ps）和缓慢（100s 的 ps）时间尺度组成。对于所有考虑的修饰，通过调整一个单一的、物理上有意义的、构象平均的量，可以在百分之几的范围内与实验结果（通过实验获得的）相吻合：NO 结合（A）和光解（A）态之间的渐近能量分离。此外，还表明，对于蛋白质的配体游离和配体结合变体，野生型与突变型 Mb 的热力学稳定性可以用相同的计算模型来描述。因此，配体动力学和热力学以直接的方式相关，类似于Φ 值分析，它建立了蛋白质折叠速率与蛋白质热稳定性之间的关系。
