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1. Characterizing the Water Wire in the Gramicidin Channel Found by Monte Carlo Sampling Using Continuum Electrostatics and in Molecular Dynamics Trajectories with Conventional or Polarizable Force Fields

   https://doi.org/10.1142/S2737416520420016  

   Zhang, Yingying; Haider, Kamran; Kaur, Divya; Ngo, Van A.; Cai, Xiuhong; Mao, Junjun; Khaniya, Umesh; Zhu, Xuyu; Noskov, Sergei; Lazaridis, Themis; et al (March 2021, Journal of Computational Biophysics and Chemistry)

   null (Ed.)

   • Water is the primary cellular solvent, yet is challenging to simulate computationally. Here we simulate water molecules in the Gramicidin A channel comparing Monte Carlo (MC) sampling with a continuum electrostatics and Molecular Dynamics (MD) calculations with the non-polarizable CHARMM36 and polarizable Drude force fields. • These give different water properties, with classical MD yielding well oriented water wires, while the Drude or continuum electrostatics force fields lead to more disordered water molecules, often changing orientation in the middle of the channel. 

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2. Progress in Lipid Droplet Simulations: How Polarizability Shapes Triacylglycerol Behavior in Bulk and Interfacial Environments

   https://doi.org/10.1021/acs.jctc.5c00882  

   Braun, R Jay; Swanson, Jessica MJ (August 2025, Journal of Chemical Theory and Computation)

   Triacylglycerols (TG) are the primary neutral lipids in lipid droplets (LDs), organelles responsible for lipid storage, metabolism, and signaling. Molecular dynamics (MD) simulations have provided valuable insight into LD structure, but fixed-charge force fields struggle to capture TG behavior across both hydrophobic cores and polar interfaces. Here, we develop and evaluate a polarizable TG model using the Drude2023 lipid force field and benchmark its performance against experimental measurements of bulk density, TG−water interfacial tension, core hydration, and monolayer expansion. The Drude model accurately reproduces the experimental properties and captures key monolayer features such as surface-oriented TGs (SURF-TGs) and chemically distinct membrane packing defects. Compared to fixed-charge models such as C36-standard and C36-cutoff, the Drude polarizable model is the only force field able to capture the dual nature of TG at polar−nonpolar interfaces like the LD monolayer and more homogeneous hydrophobic environments, like the LD core. However, C36-standard is consistent with the Drude results for the LD monolayer, while C36-cutoff is consistent with the decreased hydration in the LD core. Even with large applied surface tensions, C36-cutoff does not produce Drude-like LD monolayer properties. These results highlight the importance of dynamic polarizability and establish Drude2023 as a more reliable framework for simulating TG in heterogeneous systems like LDs. 

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3. Relative cooperativity in neutral and charged molecular clusters using QM/MM calculations

   https://doi.org/10.1063/5.0203020  

   Nochebuena, Jorge; Liu, Shubin; Cisneros, G Andrés (April 2024, The Journal of Chemical Physics)

   QM/MM methods have been used to study electronic structure properties and chemical reactivity in complex molecular systems where direct electronic structure calculations are not feasible. In our previous work, we showed that non-polarizable force fields, by design, describe intermolecular interactions through pairwise interactions, overlooking many-body interactions involving three or more particles. In contrast, polarizable force fields account partially for many-body effects through polarization, but still handle van der Waals and permanent electrostatic interactions pairwise. We showed that despite those limitations, polarizable and non-polarizable force fields can reproduce relative cooperativity achieved using density functional theory due to error compensation mechanisms. In this contribution, we assess the performance of QM/MM methods in reproducing these phenomena. Our study highlights the significance of the QM region size and force field choice in QM/MM calculations, emphasizing the importance of parameter validation to obtain accurate interaction energy predictions. 

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4. High-Order Ab Initio Valence Force Field with Chemical Pattern-Based Parameter Assignment

   https://doi.org/10.1142/S2737416521420047  

   Yang, Xudong; Liu, Chengwen; Ren, Pengyu (June 2022, Journal of Computational Biophysics and Chemistry)

   Bonded interactions are fundamental ingredients of molecular mechanics force fields because they directly determine the local structure of a molecule. In this work, we parametrize the advanced bonded energy functionals that consider the vibrational anharmonicity, the coupling effects, and the out-of-plane bending for sp2-hybridized atoms. It is expected that these models can describe the spectroscopic properties and overall structures of a molecule more accurately when they are used with polarizable AMOEBA-based force fields. 

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5. Effects of polarizability and charge transfer on water dynamics and the underlying activation energies

   https://doi.org/10.1063/5.0151253  

   Rick, Steven W.; Thompson, Ward H. (May 2023, The Journal of Chemical Physics)

   A large number of force fields have been proposed for describing the behavior of liquid water within classical atomistic simulations, particularly molecular dynamics. In the past two decades, models that incorporate molecular polarizability and even charge transfer have become more prevalent, in attempts to develop more accurate descriptions. These are frequently parameterized to reproduce the measured thermodynamics, phase behavior, and structure of water. On the other hand, the dynamics of water is rarely considered in the construction of these models, despite its importance in their ultimate applications. In this paper, we explore the structure and dynamics of polarizable and charge-transfer water models, with a focus on timescales that directly or indirectly relate to hydrogen bond (H-bond) making and breaking. Moreover, we use the recently developed fluctuation theory for dynamics to determine the temperature dependence of these properties to shed light on the driving forces. This approach provides key insight into the timescale activation energies through a rigorous decomposition into contributions from the different interactions, including polarization and charge transfer. The results show that charge transfer effects have a negligible effect on the activation energies. Furthermore, the same tension between electrostatic and van der Waals interactions that is found in fixed-charge water models also governs the behavior of polarizable models. The models are found to involve significant energy–entropy compensation, pointing to the importance of developing water models that accurately describe the temperature dependence of water structure and dynamics. 

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