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Quantitative Prediction of Charge Regulation in Oligopeptides
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
revised on 22.07.2020 and posted on 23.07.2020by 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.
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