Much of virus fate, both in the environment and in physical/chemical treatment, is dependent on electrostatic interactions. Developing an accurate means of predicting virion isoelectric point (pI) would help to understand and anticipate virus fate and transport, especially for viruses that are not readily propagated in the lab. One simple approach to predicting pI estimates the pH at which the sum of charges from ionizable amino acids in capsid proteins approaches zero. However, predicted pIs based on capsid charges frequently deviate by several pH units from empirically measured pIs. Recently, the discrepancy between empirical and predicted pI was attributed to the electrostatic neutralization of predictable polynucleotide-binding regions (PBRs) of the capsid interior. In this paper, we review models presupposing (i) the influence of the viral polynucleotide on surface charge or (ii) the contribution of only exterior residues to surface charge. We then compare these models to the approach of excluding only PBRs and hypothesize a conceptual electrostatic model that aligns with this approach. The PBR exclusion method outperformed methods based on three-dimensional (3D) structure and accounted for major discrepancies in predicted pIs without adversely affecting pI prediction for a diverse range of viruses. In addition, the PBR exclusion method was determined to be the best available method for predicting virus pI, since (i) PBRs are predicted independently of the impact on pI, (ii) PBR prediction relies on proteome sequences rather than detailed structural models, and (iii) PBR exclusion was successfully demonstrated on a diverse set of viruses. These models apply to nonenveloped viruses only. A similar model for enveloped viruses is complicated by a lack of data on enveloped virus pI, as well as uncertainties regarding the influence of the phospholipid envelope on charge and ion gradients.

中文翻译：

---

病毒等电点估计：理论与方法

无论是在环境中还是在物理/化学处理中，许多病毒的命运都取决于静电相互作用。开发一种准确的预测病毒粒子等电点（pI）的方法将有助于理解和预测病毒的命运和传播，特别是对于实验室中不容易传播的病毒。一种简单的预测pI的方法可估算衣壳蛋白中可电离氨基酸电荷总和接近零的pH。但是，基于衣壳电荷的预测pIs经常会从经验测得的pIs中偏离几个pH单位。最近，经验pI与预测的pI之间的差异归因于衣壳内部可预测的多核苷酸结合区（PBR）的静电中和。在本文中，我们回顾了以（i）病毒多核苷酸对表面电荷的影响或（ii）仅外部残基对表面电荷的影响为前提的模型。然后，我们将这些模型与仅排除PBR的方法进行比较，并假设一个与该方法一致的概念静电模型。PBR排除方法的性能优于基于三维（3D）结构的方法，并说明了预测pI的主要差异，而不会对多种病毒的pI预测产生不利影响。此外，PBR排除方法被确定为预测病毒pI的最佳方法，因为（i）PBR的预测独立于对pI的影响，（ii）PBR的预测依赖于蛋白质组序列而不是详细的结构模型，（iii）已在多种病毒中成功证明了PBR排除。这些模型仅适用于非包膜病毒。由于缺乏关于包膜病毒pI的数据，以及关于磷脂包膜对电荷和离子梯度的影响的不确定性，因此针对包膜病毒的类似模型变得复杂。