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1. Linear and Nonlinear Dielectric Response of Intrinsically Disordered Proteins

   https://doi.org/10.1021/acs.jpclett.4c00866  

   Sauer, Michael A; Colburn, Taylor; Maiti, Sthitadhi; Heyden, Matthias; Matyushov, Dmitry V (May 2024, The Journal of Physical Chemistry Letters)

   Scholes, Gregory D (Ed.)

   Linear and nonlinear dielectric responses of solutions of intrinsically disordered proteins (IDPs) were analyzed by combining molecular dynamics simulations with formal theories. A large increment of the linear dielectric function over that of the solvent is found and related to large dipole moments of IDPs. The nonlinear dielectric effect (NDE) of the IDP far exceeds that of the bulk electrolyte, offering a route to interrogate protein conformational and rotational statistics and dynamics. Conformational flexibility of the IDP makes the dipole moment statistics consistent with the gamma/log-normal distributions and contributes to the NDE through the dipole moment’s non-Gaussian parameter. The intrinsic non-Gaussian parameter of the dipole moment combines with the protein osmotic compressibility in the nonlinear dielectric susceptibility when dipolar correlations are screened by the electrolyte. The NDE is dominated by dipolar correlations when electrolyte screening is reduced. 

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2. Reorganization Energy of Electron Transfer

   https://doi.org/10.1039/d2cp06072h  

   Matyushov, Dmitry (February 2023, Physical Chemistry Chemical Physics)

   The theory of electron transfer reactions establishes the conceptual foundation for redox solution chemistry, electrochemistry, and bioenergetics. Electron and proton transfer across the cellular membrane provide all energy of life gained through natural photosynthesis and mitochondrial respiration. Rates of biological charge transfer set kinetic bottlenecks for biological energy storage. The main system-specific parameter determining the activation barrier for a single electron-transfer hop is the reorganization energy of the medium. Both harvesting of light energy in natural and artificial photosynthesis and efficient electron transport in biological energy chains require reduction of the reorganization energy to allow fast transitions. This review article discusses the mechanisms of how small values of the reorganization energy are achieved in protein electron transfer and how similar mechanisms can operate in other media, such as nonpolar and ionic liquids. One of the major mechanisms of reorganization energy reduction is through non-Gibbsian (nonergodic) sampling of the medium configurations on the reaction time. A number of alternative mechanisms, such as electrowetting of active sites of proteins, give rise to non-parabolic free energy surfaces of electron transfer. These mechanisms and nonequilibrium population of donor-acceptor vibrations lead to a universal phenomenology of separation between the Stokes-shift and variance reorganization energies of electron transfer. 

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3. Performance and Analysis of the Alchemical Transfer Method for Binding Free Energy Predictions of Diverse Ligands

   Chen Lieyang; Wu, Yujie; Wu, Chuanjie; Silveira, Ana; Sherman, Woody; Xu, Huafeng; Gallicchio, Emilio (August 2023, arXivorg)

   The Alchemical Transfer Method (ATM) is herein validated against the relative binding free energies of a diverse set of protein-ligand complexes. We employed a streamlined setup workflow, a bespoke force field, and the AToM-OpenMM software to compute the relative binding free energies (RBFE) of the benchmark set prepared by Schindler and collaborators at Merck KGaA. This benchmark set includes examples of standard small R-group ligand modifications as well as more challenging scenarios, such as large R-group changes, scaffold hopping, formal charge changes, and charge-shifting transformations. The novel coordinate perturbation scheme and a dual-topology approach of ATM address some of the challenges of single-topology alchemical relative binding free energy methods. Specifically, ATM eliminates the need for splitting electrostatic and Lennard-Jones interactions, atom mapping, defining ligand regions, and post-corrections for charge-changing perturbations. Thus, ATM is simpler and more broadly applicable than conventional alchemical methods, especially for scaffold-hopping and charge-changing transformations. Here, we performed well over 500 relative binding free energy calculations for eight protein targets and found that ATM achieves accuracy comparable to existing state-of-the-art methods, albeit with larger statistical fluctuations. We discuss insights into specific strengths and weaknesses of the ATM method that will inform future deployments. This study confirms that ATM is applicable as a production tool for relative binding free energy (RBFE) predictions across a wide range of perturbation types within a unified, open-source framework. 

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4. Statistical Mechanical Analysis of the Electromechanical Coupling in an Electrically-Responsive Polymer Chain

   https://doi.org/10.1039/D0SM00845A  

   Grasinger, Matthew; Dayal, Kaushik (January 2020, Soft Matter)

   Polymeric materials that couple deformation and electrostatics have the potential for use in soft sensors and actuators with potential applications ranging from robotic, biomedical, energy, aerospace and automotive technologies. In contrast to the mechanics of polymers that has been studied using statistical mechanics approaches for decades, the coupled response under deformation and electrical field has largely been modeled only phenomenologically at the continuum scale. In this work, we examine the physics of the coupled deformation and electrical response of an electrically-responsive polymer chain using statistical mechanics. We begin with a simple anisotropic model for the electrostatic dipole response to electric field of a single monomer, and use a separation of energy scales between the electrostatic field energy and the induced dipole field energy to reduce the nonlocal and infinite-dimensional statistical averaging to a simpler local finite-dimensional averaging. In this simplified setting, we derive the equations of the most likely monomer orientation density using the maximum term approximation, and a chain free energy is derived using this approximation. These equations are investigated numerically and the results provide insight into the physics of electro-mechanically coupled elastomer chains. Closed-form approximations are also developed in the limit of small electrical energy with respect to thermal energy; in the limit of small mechanical tension force acting on the chain; and using asymptotic matching for general chain conditions. 

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5. Nonlinear Ion-acoustic Waves, Ion Holes, and Electron Holes in the Near-Sun Solar Wind

   https://doi.org/10.3847/1538-4357/abed52  

   Mozer, F. S.; Bonnell, J. W.; Hanson, E. L. M.; Gasque, L. C.; Vasko, I. Y. (April 2021, The Astrophysical Journal)

   Abstract Nonlinear ion-acoustic waves, ion holes, and electron holes have been observed on the Parker Solar Probe at a heliocentric distance of 35 solar radii. These time domain structures contain millisecond duration electric field spikes of several mV m⁻¹. They are observed inside or at boundaries of switchbacks in the background magnetic field. Their presence in switchbacks indicates that both electron- and ion-streaming electrostatic instabilities occur there to thermalize electron and ion beams. 

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