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Heyda, J.

Publications and source records attributed to Heyda, J..

2 recordsLinked to original sources
bioRxiv2024

The Origins of Arginine "Magic": Guanidinium Like-Charge Ion Pairing and Oligoarginine Aggregation in Water by NMR, Cryoelectron Microscopy, and Molecular Dynamics Simulations

The phenomenon of like-charge pairing of hydrated ions is a physical manifestation of the unique solvation properties of certain ion pairs in water. Waters high dielectric constant and related ion screening capability significantly influence the interaction between like-charged ions, with the possibility to transform it - in some cases - from repulsion to attraction. Guanidinium cations (Gdm+) represent a quintessential example of such like-charge pairing due to their specific geometry and charge distribution. In this work, we present experimental quantification of Gdm+-Gdm+ contact ion pairing in water utilizing nuclear magnetic resonance (NMR) spectroscopy experiments complemented by molecular dynamics (MD) simulations and density functional theory (DFT) calculations. The observed interaction is very weak -- about -0.5 kJ{middle dot}mol-1 -- which aligns with theoretical estimation from MD simulations. We also contrast the behavior of Gdm+ with NH4+ cations, which do no exhibit contact ion pairing in water. DFT calculations predict that the NMR chemical shift of Gdm+ dimers is smaller than that of monomers, in agreement with NMR titration curves that display a non-linear Langmuir-like behavior. Additionally, we conducted cryo-electron microscopy experiments on oligoarginines R9, which (unlike nona-lysines K9) exhibit aggregation in water. This points again to like charge pairing of the guanidinium side chain groups, as corroborated also by molecular dynamics simulations of these peptides in water.

biophysics↗
bioRxiv2024

Effective Inclusion of Electronic Polarization Improves the Description of Electrostatic Interactions: The prosECCo75 Biomolecular Force Field

prosECCo75 is an optimized force field effectively incorporating electronic polarization via charge scaling. It aims to enhance the accuracy of nominally nonpolarizable molecular dynamics (MD) simulations for interactions in biologically relevant systems involving water, ions, proteins, lipids, and saccharides. Recognizing the inherent limitations of nonpolarizable force fields in precisely modeling electrostatic interactions essential for various biological processes, we mitigate these shortcomings by accounting for electronic polarizability in a physical rigorous mean-field way that does not add to computational costs. With this scaling of (both integer and partial) charges within the CHARMM36 framework, prosECCo75 addresses overbinding artifacts. This improves agreement with experimental ion binding data across a broad spectrum of systems -- lipid membranes, proteins (including peptides and amino acids), and saccharides -- without compromising their biomolecular structures. prosECCo75 thus emerges as a computationally efficient tool providing enhanced accuracy and broader applicability in simulating the complex interplay of interactions between ions and biomolecules, pivotal for improving our understanding of many biological processes.

biophysics↗