Quantitative Prediction of pH-Controlled Ionization of Oligopeptides

Weak ampholytes are ubiquitous in nature and commonly found in artificial pH-responsive systems. However, our limited understanding of their ionisation response 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. Differences in ionisation response between oligopeptides and monomeric amino acids showed that electrostatic interactions between weak acid and base side chains play a key role in oligopeptide ionisation, as predicted by our model. Moreover, by comparing our simulations with experimental results from potentiometric titration, capillary zone electrophoresis and NMR, we demonstrated that our model reliably predicts the ionisation response and electrophoretic mobilities of various peptide sequences. Ultimately, our model is the first step towards using predictive bottom-up design of responsive ampholytes to tailor their properties as a function of charge and pH.

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Quantitative Prediction of Charge Regulation in Oligopeptides

10.26434/chemrxiv.12501470.v3 ◽

2020 ◽

Author(s):

Raju Lunkad ◽

Anastasiia Murmiliuk ◽

Pascal Hebbeker ◽

Milan Boublík ◽

Zdeněk Tošner ◽

...

Keyword(s):

Electrostatic Interactions ◽

Weak Acid ◽

Coarse Grained ◽

Disordered Proteins ◽

Quantitative Prediction ◽

Bottom Up ◽

Charge Regulation ◽

Flexible Polymer ◽

Acid And Base ◽

Base Side

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.

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Quantitative Prediction of Charge Regulation in Oligopeptides

10.26434/chemrxiv.12501470.v4 ◽

2020 ◽

Author(s):

Raju Lunkad ◽

Anastasiia Murmiliuk ◽

Pascal Hebbeker ◽

Milan Boublík ◽

Zdeněk Tošner ◽

...

Keyword(s):

Electrostatic Interactions ◽

Weak Acid ◽

Coarse Grained ◽

Disordered Proteins ◽

Quantitative Prediction ◽

Bottom Up ◽

Charge Regulation ◽

Flexible Polymer ◽

Acid And Base ◽

Base Side

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.

Download Full-text

Quantitative Prediction of Charge Regulation in Oligopeptides

10.26434/chemrxiv.12501470 ◽

2020 ◽

Author(s):

Raju Lunkad ◽

Anastasiia Murmiliuk ◽

Pascal Hebbeker ◽

Milan Boublík ◽

Zdeněk Tošner ◽

...

Keyword(s):

Electrostatic Interactions ◽

Weak Acid ◽

Coarse Grained ◽

Disordered Proteins ◽

Quantitative Prediction ◽

Bottom Up ◽

Charge Regulation ◽

Flexible Polymer ◽

Acid And Base ◽

Base Side

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.

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A new one-site coarse-grained model for water: Bottom-up many-body projected water (BUMPer). II. Temperature transferability and structural properties at low temperature

The Journal of Chemical Physics ◽

10.1063/5.0026652 ◽

2021 ◽

Vol 154 (4) ◽

pp. 044105

Author(s):

Jaehyeok Jin ◽

Alexander J. Pak ◽

Yining Han ◽

Gregory A. Voth

Keyword(s):

Low Temperature ◽

Structural Properties ◽

Coarse Grained ◽

Many Body ◽

Bottom Up ◽

Coarse Grained Model ◽

Water Bottom

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Adsorption of Lysozyme Into a Charged Confining Pore

10.1101/2021.07.11.451934 ◽

2021 ◽

Author(s):

Sidney Carvalho ◽

Ralf Metzler ◽

Andrey Cherstvy ◽

Daniel Caetano

Keyword(s):

Electrostatic Interactions ◽

Active Sites ◽

Coarse Grained ◽

Pore Surface ◽

Solution Ph ◽

Coarse Grained Model ◽

Egg White Lysozyme ◽

Constant Ph ◽

Pka Shift ◽

Effects Of Ph

Several applications arise from the confinement of proteins on surfaces since their stability and biological activity are enhanced. It is also known that the way a protein adsorbs on the surface is important for its biological function since its active sites should not be obstructed. In this study, the adsorption properties of hen egg-white Lysozyme, HEWL, into a negatively charged silica pore is examined employing a coarse-grained model and constant-pH Monte Carlo simulations. The role of electrostatic interactions is taken into account when including the Debye-Hueckel potentials into the Ca structure-based model. We evaluate the effects of pH, salt concentration, and pore radius on the protein preferential orientation and spatial distribution of its residues regarding the pore surface. By mapping the residues that stay closer to the pore surface, we find the increase of pH leads to orientational changes of the adsorbed protein when the solution pH gets closer to the HEWL isoelectric point. At these conditions, the pKa shift of these important residues caused by the adsorption into the charged confining surface results in a HEWL charge distribution that stabilizes the adsorption in the observed protein orientation. We compare our observations to the results of pKa shift for HEWL available in the literature and to some experimental data.

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Sequence-dependent Three Interaction Site (TIS) Model for Single and Double-stranded DNA

10.1101/256487 ◽

2018 ◽

Cited By ~ 1

Author(s):

Debayan Chakraborty ◽

Naoto Hori ◽

D. Thirumalai

Keyword(s):

Electrostatic Interactions ◽

Persistence Length ◽

Data Bank ◽

Coarse Grained ◽

Force Extension ◽

Sequence Dependence ◽

Coarse Grained Model ◽

Interaction Sites ◽

Double Stranded Dna ◽

Centers Of Mass

AbstractWe develop a robust coarse-grained model for single and double stranded DNA by representing each nucleotide by three interaction sites (TIS) located at the centers of mass of sugar, phosphate, and base. The resulting TIS model includes base-stacking, hydrogen bond, and electrostatic interactions as well as bond-stretching and bond angle potentials that account for the polymeric nature of DNA. The choices of force constants for stretching and the bending potentials were guided by a Boltzmann inversion procedure using a large representative set of DNA structures extracted from the Protein Data Bank. Some of the parameters in the stacking interactions were calculated using a learning procedure, which ensured that the experimentally measured melting temperatures of dimers are faithfully reproduced. Without any further adjustments, the calculations based on the TIS model reproduces the experimentally measured salt and sequence dependence of the size of single stranded DNA (ssDNA), as well as the persistence lengths of poly(dA) and poly(dT) chains. Interestingly, upon application of mechanical force the extension of poly(dA) exhibits a plateau, which we trace to the formation of stacked helical domains. In contrast, the force-extension curve (FEC) of poly(dT) is entropic in origin, and could be described by a standard polymer model. We also show that the persistence length of double stranded DNA, formed from two complementary ssDNAs with one hundred and thirty base pairs, is consistent with the prediction based on the worm-like chain. The persistence length, which decreases with increasing salt concentration, is in accord with the Odijk-Skolnick-Fixman theory intended for stiff polyelectrolyte chains near the rod limit. The range of applications, which did not require adjusting any parameter after the initial construction based solely on PDB structures and melting profiles of dimers, attests to the transferability and robustness of the TIS model for ssDNA and dsDNA.

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Coarse-grained dynamic RNA titration simulations

Interface Focus ◽

10.1098/rsfs.2018.0066 ◽

2019 ◽

Vol 9 (3) ◽

pp. 20180066 ◽

Cited By ~ 2

Author(s):

S. Pasquali ◽

E. Frezza ◽

F. L. Barroso da Silva

Keyword(s):

Electrostatic Interactions ◽

Molecular Organization ◽

Coarse Grained ◽

Solution Ph ◽

Dynamic Simulations ◽

Rna Molecules ◽

Coarse Grained Model ◽

Constant Ph ◽

Conformational Plasticity ◽

And Function

Electrostatic interactions play a pivotal role in many biomolecular processes. The molecular organization and function in biological systems are largely determined by these interactions. Owing to the highly negative charge of RNA, the effect is expected to be more pronounced in this system. Moreover, RNA base pairing is dependent on the charge of the base, giving rise to alternative secondary and tertiary structures. The equilibrium between uncharged and charged bases is regulated by the solution pH, which is therefore a key environmental condition influencing the molecule’s structure and behaviour. By means of constant-pH Monte Carlo simulations based on a fast proton titration scheme, coupled with the coarse-grained model HiRE-RNA, molecular dynamic simulations of RNA molecules at constant pH enable us to explore the RNA conformational plasticity at different pH values as well as to compute electrostatic properties as local p K a values for each nucleotide.

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Concentration-dependent swelling and structure of ionic microgels: simulation and theory of a coarse-grained model

Soft Matter ◽

10.1039/c8sm00799c ◽

2018 ◽

Vol 14 (22) ◽

pp. 4530-4540 ◽

Cited By ~ 12

Author(s):

Tyler J. Weyer ◽

Alan R. Denton

Keyword(s):

Structural Properties ◽

Electrostatic Interactions ◽

Coarse Grained ◽

Coarse Grained Model

Swelling and structural properties of ionic microgel suspensions are described by a coarse-grained model that includes elastic and electrostatic interactions.

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A Coarse Grained Model for DNA and Polymer Packaging: Statics and Dynamics

Journal of Theoretical Medicine ◽

10.1080/10273660500149927 ◽

2005 ◽

Vol 6 (2) ◽

pp. 115-117 ◽

Cited By ~ 3

Author(s):

I. Ali ◽

D. Marenduzzo ◽

C. Micheletti ◽

J. M. Yeomans

Keyword(s):

Coarse Grained ◽

Viral Capsids ◽

Coarse Grained Model ◽

Flexible Polymer ◽

Numerical Characterization ◽

Bacteriophage Genome ◽

Statics And Dynamics ◽

Dynamical Features ◽

Semi Flexible Polymer

We present a numerical characterization of the statics and dynamics of the packaging of a semi-flexible polymer inside a sphere. The study is motivated by recent experiments on the packaging of DNA inside viral capsids. It is found that the force required to confine the coarse-grained polymer is in fair agreement with that found in experiments for the packaging of the phi29 bacteriophage genome. Despite its schematic nature, the model is capable of reproducing the most salient dynamical features of packaging experiments such as the presence of pauses during individual packaging processes and the trend of the resisting force as a function of chain packed fraction.

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