Site Correlations, Capacitance, and Polarizability From Protein Protonation Fluctuations

Božič, Anže; Podgornik, Rudolf

doi:10.1021/acs.jpcb.1c08200

Cited by 5 publications

(4 citation statements)

References 45 publications

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“…A very useful observable to quantify the capacity of a weak PE to regulate its charge is the quantity

which measures the response of the degree of protonation to changes in the pH-value, in a similar way to how heat capacity quantifies the energy changes when modifying the temperature. C has been given many names in the literature such as (protein/charge/differential/ proton/binding) capacitance [ 6 , 37 , 63 , 67 , 68 , 69 ], charge regulation parameter [ 70 ] and charge regulation capacity [ 71 ]. Among them, we choose charge regulation capacity to avoid possible confusions with the term “capacitance” used in electrochemistry.…”

Section: Fundamental Concepts On Weak Polyelectrolytesmentioning

confidence: 99%

Unusual Aspects of Charge Regulation in Flexible Weak Polyelectrolytes

et al. 2023

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This article reviews the state of the art of the studies on charge regulation (CR) effects in flexible weak polyelectrolytes (FWPE). The characteristic of FWPE is the strong coupling of ionization and conformational degrees of freedom. After introducing the necessary fundamental concepts, some unconventional aspects of the the physical chemistry of FWPE are discussed. These aspects are: (i) the extension of statistical mechanics techniques to include ionization equilibria and, in particular, the use of the recently proposed Site Binding-Rotational Isomeric State (SBRIS) model, which allows the calculation of ionization and conformational properties on the same foot; (ii) the recent progresses in the inclusion of proton equilibria in computer simulations; (iii) the possibility of mechanically induced CR in the stretching of FWPE; (iv) the non-trivial adsorption of FWPE on ionized surfaces with the same charge sign as the PE (the so-called “wrong side” of the isoelectric point); (v) the influence of macromolecular crowding on CR.

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“…A very useful observable to quantify the capacity of a weak PE to regulate its charge is the quantity

Section: Fundamental Concepts On Weak Polyelectrolytesmentioning

confidence: 99%

Unusual Aspects of Charge Regulation in Flexible Weak Polyelectrolytes

et al. 2023

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“…Protonation and proton transfer play critical roles in the stability, function, and regulation of biomolecular processes. − Since protonation and deprotonation can drastically change the electrostatic properties of the target group, as such the term “ionization” is often used to reflect the net charge change, a combination of multiple protonation groups in protein and other biomolecules provides a convenient and often refined means to stabilize the protein structure and achieve the delicate functions. − The physical chemistry of the ionization processes has attracted great attention from the very early biochemical researchers and remains to be an intensively studied topic today. , …”

mentioning

confidence: 99%

“…5−8 The physical chemistry of the ionization processes has attracted great attention from the very early biochemical researchers 9 and remains to be an intensively studied topic today. 10,11 Theoretical study of protein protonation faces several technical challenges. These include, but are not limited to, 12−15 a method to accurately compute the bond formation/dissociation energy; an energy function to accurately describe the solvation effect; sufficient phase space samplings to take into account the contribution of the protein conformational fluctuations; and last but not least, the site−site coupling between different protonation groups that creates a large number of different ionization/protonation states.…”

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Quantum Computer Simulation of Protein Protonation

2023

J. Chem. Theory Comput.

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In attempts to simulate the protonation of proteins, a major challenge is that the number of protonation states grows rapidly as a function (2 N ) of the number of protonation sites (N). Expression on the free energy of the protonation state as an N-site Ising model � using an empirical Generalized-Born model � allows a quantum computer to efficiently determine the important states at a given pH value and subsequently reconstruct the pH titration process at all sites. Compared with the exact results painstakingly obtained with classical computers, the results obtained using quantum computers show good agreement for staphylococcal nuclease and excellent agreement for αlactalbumin. This work illustrates the effectiveness of quantum computers in sampling important physical states, which may be useful in attacking challenging biomolecular problems.

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Both Charge-Regulation and Charge-Patch Distribution Can Drive Adsorption on the Wrong Side of the Isoelectric Point

2022

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The mechanism of protein–polyelectrolyte complexation on the wrong side of the isoelectric point has long puzzled researchers. Two alternative explanations have been proposed in the literature: (a) the charge-patch (CP) mechanism, based on the inhomogeneous distribution of charges on the protein, and (b) the charge-regulation (CR) mechanism, based on the variable charge of weak acid and base groups, which may invert the protein charge in the presence of another highly charged object. To discern these two mechanisms, we simulated artificially constructed short peptides, containing acidic and basic residues, arranged in a blocklike or alternating sequence. Our simulations of these peptides, interacting with polyelectrolytes, showed that charge patch and charge regulation alone can both lead to adsorption on the wrong side of the pI value. Their simultaneous presence enhances adsorption, whereas their absence prevents adsorption. Our simulation results were rationalized by following the variation of the charge regulation capacity and dipole moments of these peptides with the pH. Specifically for lysozyme, we found that charge patch prevails at physiological pH, whereas charge regulation prevails near the pI, thereby explaining seemingly contradicting conclusions in the literature. By applying the same approach to other proteins, we developed a general framework for assessing the role of the CP and CR mechanisms in existing case studies and for predicting how various proteins interact with polyelectrolytes at different pH values.

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Site Correlations, Capacitance, and Polarizability From Protein Protonation Fluctuations

Cited by 5 publications

References 45 publications

Unusual Aspects of Charge Regulation in Flexible Weak Polyelectrolytes

Unusual Aspects of Charge Regulation in Flexible Weak Polyelectrolytes

Quantum Computer Simulation of Protein Protonation

Both Charge-Regulation and Charge-Patch Distribution Can Drive Adsorption on the Wrong Side of the Isoelectric Point

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