DEP is an established method to manipulate micrometer-sized particles, but standard continuum theories predict only negligible effects for nanometer-sized proteins despite contrary experimental evidence. A theoretical description of protein DEP needs to consider details on the molecular scale. Previous work toward this goal addressed the role of orientational polarization of static protein dipole moments for dielectrophoretic effects, which successfully predicts the general magnitude of dielectrophoretic forces on proteins but does not readily explain negative DEP forces observed for proteins in some experiments. However, contributions to the protein chemical potential due to protein–water interactions have not yet been considered in this context. Here, we utilize atomistic molecular dynamics simulations to evaluate polarization-induced changes in the protein solvation free energy, which result in a solvent-mediated contribution to dielectrophoretic forces. We quantify solvent-mediated dielectrophoretic forces for two proteins and a small peptide in water, which follow expectations for protein–water dipole–dipole interactions. The magnitude of solvent-mediated dielectrophoretic forces exceeds predictions of nonmolecular continuum theories, but plays a minor role for the total dielectrophoretic force for the simulated proteins due to dominant contributions from the orientational polarization of their static protein dipoles. However, we extrapolate that solvent-mediated contributions to negative protein DEP forces will become increasingly relevant for multidomain proteins, complexes and aggregates with large protein–water interfaces, as well as for high electric field frequencies, which provides a potential mechanism for corresponding experimental observations of negative protein DEP.

中文翻译：

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蛋白质介电泳中的溶剂介导力

DEP 是一种操作微米级粒子的既定方法，但标准的连续统理论预测对纳米级蛋白质的影响可以忽略不计，尽管有相反的实验证据。蛋白质 DEP 的理论描述需要考虑分子尺度的细节。以前朝着这个目标开展的工作解决了静态蛋白质偶极矩的定向极化对介电泳效应的作用，这成功地预测了蛋白质上介电泳力的一般大小，但不容易解释在某些实验中观察到的蛋白质的负 DEP 力。然而，在这种情况下尚未考虑由于蛋白质 - 水相互作用对蛋白质化学势的贡献。这里，我们利用原子分子动力学模拟来评估极化引起的蛋白质溶剂化自由能的变化，这导致溶剂介导的介电泳力的贡献。我们量化了水中两种蛋白质和一种小肽的溶剂介导的介电泳力，这符合蛋白质-水偶极-偶极相互作用的预期。溶剂介导的介电泳力的大小超过了非分子连续体理论的预测，但由于其静态蛋白质偶极子的定向极化的主要贡献，对模拟蛋白质的总介电泳力起着次要作用。然而，我们推断溶剂介导的对负蛋白 DEP 力的贡献将越来越与多域蛋白相关，