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Quantitative Prediction of Charge Regulation in Oligopeptides

revised on 22.07.2020 and posted on 23.07.2020 by Raju Lunkad, Anastasiia Murmiliuk, Pascal Hebbeker, Milan Boublík, Zdeněk Tošner, Miroslav Štěpánek, Peter Košovan
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.


Czech Science Foundation, grant 19-10429S

Grant agency of the Charles University, grant GAUK 978218

Ministry of Education, Youth and Sports of the Czech Republic, Operational Programme Research, Development and Education: “Excellent Research Teams”, Project No. CZ.02.1.01/0.0/0.0/15_003/0000417-CUCAM

e-INFRA LM2018140


Email Address of Submitting Author


Charles University


Czech Republic

ORCID For Submitting Author


Declaration of Conflict of Interest

Nothing to declare.

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