Thermodynamics and the solvent role in the acceleration of the Diels–Alder reaction between cyclopentadiene (CPD) and methyl vinyl ketone (MVK) have been revisited. In this work we use an ab initio hybrid QM/MM-MD scheme combined with multiple steered molecular dynamics to extract the free energy pofile in water and methanol using the bidirectional Minh–Adib estimator. We obtain 18.7 kcal mol–1 and 20.8 kcal mol–1 free energy barrier for the reaction in water and methanol, respectively. This methodology reproduces experimental values with an absolute error of about 0.8 kcal mol–1. The experimental difference between the activation free-energy barriers of water and methanol is also reproduced with an absolute error of about 0.1 kcal mol–1. We explore the charge transfer evolution along reaction coordinates to characterize the electronic behavior for this reaction. It is shown that the solvent molecules around the reaction system produce a global polarization along the reaction coordinate which is consistent with the solvent polarity. The results highlight the role of hydrogen bonding formed in the transition state to stabilize the system charge reorganization in the reaction process.
Metal cations are ubiquitous components in biological environments and play an important role in regulating cellular functions and membrane properties. By applying metadynamics simulations, we have performed systematic free energy calculations of Na+, K+, Ca2+, and Mg2+ bound to phospholipid membrane surfaces for the first time. The free energy landscapes unveil specific binding behaviors of metal cations on phospholipid membranes. Na+ and K+ are more likely to stay in the aqueous solution and can bind easily to a few lipid oxygens by overcoming low free energy barriers. Ca2+ is most stable when it is bound to four lipid oxygens of the membrane rather than being hydrated in the aqueous solution. Mg2+ is tightly hydrated, and it shows hardly any loss of a hydration water or binding directly to the membrane. When bound to the membrane, the cations’ most favorable total coordination numbers with water and lipid oxygens are the same as their corresponding hydration numbers in aqueous solution, indicating a competition between ion binding to water and lipids. The binding specificity of metal cations on membranes is highly correlated with the hydration free energy and the size of the hydration shell.
Local stress fields are routinely computed from molecular dynamics trajectories to understand the structure and mechanical properties of lipid bilayers. These calculations can be systematically understood with the Irving-Kirkwood-Noll theory. In identifying the stress tensor, a crucial step is the decomposition of the forces on the particles into pairwise contributions. However, such a decomposition is not unique in general, leading to an ambiguity in the definition of the stress tensor, particularly for multibody potentials. Furthermore, a theoretical treatment of constraints in local stress calculations has been lacking. Here, we present a new implementation of local stress calculations that systematically treats constraints and considers a privileged decomposition, the central force decomposition, that leads to a symmetric stress tensor by construction. We focus on biomembranes, although the methodology presented here is widely applicable. Our results show that some unphysical behavior obtained with previous implementations (e.g. nonconstant normal stress profiles along an isotropic bilayer in equilibrium) is a consequence of an improper treatment of constraints. Furthermore, other valid force decompositions produce significantly different stress profiles, particularly in the presence of dihedral potentials. Our methodology reveals the striking effect of unsaturations on the bilayer mechanics, missed by previous stress calculation implementations.
In this article, the interaction between a methane molecule and a graphene plane in liquid water has been characterized employing DFT-based free energy Molecular Dynamics calculations. This system represents a good model to understand the generic interaction between a small hydrophobic solute (methane molecule) and an extense hydrophobic surface (graphene plane). The structural and dynamical properties of graphene and methane hydration water are analyzed and found to be closely related to the main features of the potential of mean force. The results could be used in coarse-grained models to take into account the effect of the hydrophobic interaction in realistic systems relevant to experiment.
The high polarizability of halide anions affects, in aqueous solutions, many phenomena ranging from hydrogen bond dynamics to water interfaces’ structure. In this Letter dipolar interactions of halides in water are investigated through Car-Parrinello Molecular Dynamics simulations. Contrary to previous studies, a different polarization of first and second hydration shell water molecules is found. The analysis hints that existing classical polarizable force fields lack a description of short-range interactions which causes an overestimation of polarization effects.