Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas 77555, United States.
J Phys Chem B. 2022 Jun 23;126(24):4543-4554. doi: 10.1021/acs.jpcb.2c01611. Epub 2022 Jun 13.
In this work, the components of the protein electrostatic potentials in solution are analyzed with NMR paramagnetic relaxation enhancement experiments and compared with continuum solution theory, and multiscale simulations. To determine the contributions of the solution components, we analyze them at different ionic strengths from 0 to 745 mM. A theoretical approximation allows the determination of the electrostatic potential at a given proton without reference to the protein structure given the ratio of paramagnetic relaxation enhancements rates between a cationic and an anionic probe. The results derived from simulations show good agreement with experiment and simple continuum solvent theory for many of the residues. A discrepancy including a switch of sign of the electrostatic potential was observed for particular residues. By considering the components of the potential, we found the discrepancy is mainly caused by angular correlations of the probe molecules with these residues. The correction for the correlations allows a more accurate analysis of the experiments determining the electrostatic potential of proteins in solution.
在这项工作中，我们通过 NMR 顺磁弛豫增强实验分析了蛋白质静电势在溶液中的组成，并与连续溶液理论和多尺度模拟进行了比较。为了确定溶液成分的贡献，我们在 0 到 745mM 的不同离子强度下对它们进行了分析。一种理论近似允许在给定质子的情况下确定静电势，而无需参考蛋白质结构，只要给出阳离子和阴离子探针之间的顺磁弛豫增强率的比值即可。模拟得出的结果与实验和简单的连续溶剂理论在许多残基上都吻合得很好。然而，对于某些特定的残基，我们观察到了一个差异，包括静电势的符号发生了转变。通过考虑电势的组成部分，我们发现这种差异主要是由于探针分子与这些残基之间的角相关性引起的。对相关性的修正可以更准确地分析实验，从而确定蛋白质在溶液中的静电势。
