Quantitative Prediction of Charge Regulation in Oligopeptides

23 July 2020, Version 3
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Weak ampholytes are ubiquitous in nature and commonly found in artificial pH-responsive systems. However, our limited understanding of their charge regulation and the lack of predictive capabilities hinder the bottom-up design of such systems. Here, we used a coarse-grained model of a flexible polymer with weakly ionisable monomer units to quantitatively analyse the ionisation behaviour of two oligopeptides. Our model predicts differences in the charge states between oligopeptides and monomeric amino acids, showing that conformational flexibility and electrostatic interactions between weak acid and base side chains play a key role in the charge regulation. By comparing our simulations with experimental results from potentiometric titration, capillary zone electrophoresis and NMR, we demonstrated that our model reliably predicts the charge state of various peptide sequences. Ultimately, our model is the first step towards understanding the charge regualtion in flexible disordered proteins, and towards using predictive bottom-up design of responsive ampholytes to tailor their
properties as a function of charge and pH.

Keywords

peptide
ampholyte
ionization
acid-base
simulation
constant-pH ensemble
pH-responsive
polyelectrolyte
coarse-grained
charge regulation

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.