Zheng Yi, Chen Taoyi, Vaissier Welborn Valerie
Department of Chemistry, Virginia Tech, Blacksburg, VA, 24061, USA.
Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061, USA.
Chembiochem. 2025 May 27;26(10):e202500314. doi: 10.1002/cbic.202500314. Epub 2025 May 21.
Enzymes are reported to catalyze reactions by generating electric fields that promote the evolution of the reaction in the active site. Although seldom used outside enzymatic catalysis, electrostatic preorganization theory and language of electric fields can be generalized to other biological macromolecules. Herein, we performed molecular dynamics simulations of human Na1.5, Na1.6, and Na1.7 with the atomic multipole optmimized energetics for biomolecular applications polarizable force field. We show that in the absence of an external potential, charged and uncharged residues generate strong electric fields that assist in Na motion in the pore. This work emphasizes the importance of charge-dipole interactions in modulating Na dynamics, in addition to charge-charge interactions, the focus of a majority of previous studies. Finally, we find that residues share a high level of mutual information through electric fields that can enable the optimization of allosteric pathways.
据报道，酶通过产生促进活性位点反应进程的电场来催化反应。尽管在酶催化之外很少使用，但静电预组织理论和电场语言可以推广到其他生物大分子。在此，我们使用用于生物分子应用的原子多极优化能量极化力场对人类Na1.5、Na1.6和Na1.7进行了分子动力学模拟。我们表明，在没有外部电势的情况下，带电和不带电残基会产生强电场，有助于钠离子在孔中的移动。这项工作强调了电荷 - 偶极相互作用在调节钠动力学中的重要性，除了电荷 - 电荷相互作用之外，而电荷 - 电荷相互作用是大多数先前研究的重点。最后，我们发现残基通过电场共享高水平的互信息，这可以实现变构途径的优化。
