Molecular Dynamics Simulations Using a Capacitance–Polarizability Force Field

We present molecular dynamics (MD) simulations using a capacitance–polarizability force field. This force field allows an atomistic description of charge migration within a particle and hence the image charge effects at the interface of such a particle. By employing atomic capacitance and polarizability as the key parameters that describe fluctuating charges and dipoles, we can thus explore the effect of charge migration on the structural dynamics. We illustrate the method by exploring gold nanoparticles in aqueous solutions and compare with previous simulation work. We reach the conclusion that the capacitance–polarizability force field MD method serves as a promising tool for simulating gold–water systems, indicating probable extensions to other metal solutions and for studies of more complicated systems provided that a proper parametrization of the capacitance force field can be made. For the particular system studied, it is found that the water molecules interact with the surface through oxygen atoms, leading to more hydrogen-bond donors than acceptors at the gold–water interface. A prominent shoulder peak is found in the radial distribution of oxygen atoms with respect to the gold surface, due to the fact that the oxygen atoms adsorbed at the on-top sites of the gold nanoparticle. The surface of the aqueous gold nanoparticle carries negative charge, which is balanced by the positive charge in the second outermost layer

Simulation of Gold Functionalization with Cysteine by Reactive Molecular Dynamics

The anchoring mechanism of cysteine to gold in water solution is characterized in detail by means of a combination of quantum chemistry (QC) and reactive classical molecular dynamics (RC-MD) calculations. A possible adsorption–reaction route is proposed, through RC-MD simulations based on a modified version of the protein reactive force field (ReaxFF), in which gold–protein interactions have been included after accurate parametrization at the QC level. The computational results confirm recent experimental findings regarding the mechanism as a two-step binding, namely, a slow physisorption followed by a fast chemisorption. The reaction barriers are estimated through the nudged elastic band approach and checked by QC calculations. Surface reconstructions, induced by the strong adsorption of the molecule, are identified, and their role, as further adsorbate stabilizers, is properly disclosed. The satisfactory agreement with QC data and experiments confirm the reliability of the simulations and the unique opportunity they provide to follow locally molecule adsorption on selected materials

Functional Water Molecules in Rhodopsin Activation

G-protein-coupled receptors (GPCRs) are integral membrane proteins that mediate cellular response to an extensive variety of extracellular stimuli. Studies of rhodopsin, a prototype GPCR, have suggested that water plays an important role in mediating the activation of family A GPCRs. However, our understanding of the function of water molecules in the GPCR activation is still rather limited because resolving the functional water molecules solely based on the results from existing experiments is challenging. Using all-atom molecular dynamics simulations in combination with inhomogeneous fluid theory, we identify in this work the positioning of functional water molecules in the inactive state, the Meta II state, and the constitutive active state of rhodopsin, basing on the thermodynamic signatures of the water molecules. We find that one hydration site likely functions as a switch to regulate the distance between Glu181 and the Schiff base in the rhodopsin activation. We observe that water molecules adjacent to the “NpxxY” motif are not as stable in the Meta II state as in the inactive state as indicated by the thermodynamics signatures, and we rationalize that the behaviors of these water molecules are closely correlated with the rearrangement of the water-mediated hydrogen-bond network in the “NPxxY” motif, which is essential for mediating the activation of the receptor. We thereby propose a hypothesis of the water-mediated rhodopsin activation pathway

Two-Photon Absorption of Metal-Assisted Chromophores

Aiming to understand the effect of a metal surface on nonlinear optical properties and the combined effects of surface and solvent environments on such properties, we present a multiscale response theory study, integrated with dynamics of the two-photon absorption of 4-nitro-4′-amino-<i>trans</i>-stilbene physisorbed on noble metal surfaces, considering two such surfaces, Ag(111) and Au(111), and two solvents, cyclohexane and water, as cases for demonstration. A few conclusions of general character could be drawn: While the geometrical change of the chromophore induced by the environment was found to notably alter (diminish) the two-photon absorption cross section in the polar medium, the effects of the metal surface and solvent on the electronic structure of the chromophore surpasses the geometrical effects and leads to a considerably enhanced two-photon absorption cross section in the polar solvent. This enhancement of two-photon absorption arises essentially from the metal charge image induced enlargement of the difference between the dipole moment of the excited state and the ground state. The orientation-dependence of the two-photon absorption is found to connect with the lateral rotation of the chromophore, where the two-photon absorption reaches its maximum when the polarization of the incident light coincides with the long-axis of the chromophore. Our results demonstrate a distinct enhancement of the two-photon absorption by a metal surface and a polar medium and envisage the employment of metal–chromophore composite materials for future development of nonlinear optical materials with desirable properties

First Hyperpolarizability of Collagen Using the Point Dipole Approximation

The application of localized hyperpolarizabilities to predict a total protein hyperpolarizability is presented for the first time, using rat-tail collagen as a demonstration example. We employ a model comprising the quadratic Applequist point-dipole approach, the so-called LoProp transformation, and a procedure with molecular fractionation using conjugate caps to determine the atomic and bond contributions to the net β tensor of the collagen [(PPG)₁₀]₃ triple-helix. By using Tholes exponential damping modification to the dyadic tensor in the Applequist equations, a correct qualitative agreement with experiment is found. The intensity of the β_HRS signal and the depolarization ratios are best reproduced by decomposing the LoProp properties into the atomic positions and using Tholes exponential damping with the original damping parameter. Some ramifications of the model for general protein property optimization are briefly discussed

Microsecond Molecular Dynamics Simulations Provide Insight into the Allosteric Mechanism of the Gs Protein Uncoupling from the β₂ Adrenergic Receptor

Experiments have revealed that in the β₂ adrenergic receptor (β₂AR)–Gs protein complex the α subunit (Gαs) of the Gs protein can adopt either an “open” conformation or a “closed” conformation. In the “open” conformation the Gs protein prefers to bind to the β₂AR, while in the “closed” conformation an uncoupling of the Gs protein from the β₂AR occurs. However, the mechanism that leads to such different behaviors of the Gs protein remains unclear. Here, we report results from microsecond molecular dynamics simulations and community network analysis of the β₂AR–Gs complex with Gαs in the “open” and “closed” conformations. We observed that the complex is stabilized differently in the “open” and “closed” conformations. The community network analysis reveals that in the “closed” conformation there exists strong allosteric communication between the β₂AR and Gβγ, mediated by Gαs. We suggest that such high information flows are necessary for the Gs protein uncoupling from the β₂AR

Photochromic Diarylethenes with Heterocyclic Aromatic Rings: Correlation between Thermal Bistability and Geometrical Characters of Transition States

We present a density functional theory study on the thermal bistability of a number of photochromic diarylethenes, with emphasis on the free energy barrier of the ground-state ring-opening process. We found that the free energy barrier is correlated with the geometrical and vibrational character of the transition state, in particular the distance between the two reactive carbon atoms, the out-of-plane angles of the methyl groups at the reactive carbon atoms, and the imaginary vibrational frequency. Based on these relationships we propose a linear fitting expression for the free energy barrier in terms of the three aforementioned transition-state quantities and obtained a correlation coefficient of <i>R</i>² = 0.971. In this way quantum chemical calculations may provide insight and structure–property relationships, which can be applied in the development of novel photochromic materials

Electronic Circular Dichroism of Surface-Adsorbed Molecules by Means of Quantum Mechanics Capacitance Molecular Mechanics

To promote a more comprehensive understanding of the influence of metal–adsorbate interaction for molecules at metallo surfaces or metallo nanoparticles in solvent environments on their electronic circular dichroism (ECD) spectra, we evaluate the application of a recently derived quantum mechanics capacitance molecular mechanics (QMCMM) model for ECD. Using helicene absorbed on gold surfaces in protic and aprotic solvents as illustration, we elucidate the detailed effects on excitation energies, transition moments, rotatory strengths, orientation dependence of ECD spectra, and the different roles of aprotic and protic solvents and the induced charge distribution patterns on the surface. These changes are decomposed in terms of surface alone, solvent alone, and combined surface–solvent influence, and furthermore into the indirect contributions by the surface-induced restructuring of the helicene. Much of the salient changes of the ECD can be rationalized to the substantial redistribution of charge at the gold surface induced by the presence of the helicene. The study indicates that through the QMCMM model the effects of a metallic surface on the circular dichroism spectra of adsorbed organic molecules can be tackled by extended QM calculations coupled to polarizability–capacitance force fields for large metallic clusters representing surfaces or nanoparticles

Simulation of Gold Functionalization with Cysteine by Reactive Molecular Dynamics

The anchoring mechanism of cysteine to gold in water solution is characterized in detail by means of a combination of quantum chemistry (QC) and reactive classical molecular dynamics (RC-MD) calculations. A possible adsorption–reaction route is proposed, through RC-MD simulations based on a modified version of the protein reactive force field (ReaxFF), in which gold–protein interactions have been included after accurate parametrization at the QC level. The computational results confirm recent experimental findings regarding the mechanism as a two-step binding, namely, a slow physisorption followed by a fast chemisorption. The reaction barriers are estimated through the nudged elastic band approach and checked by QC calculations. Surface reconstructions, induced by the strong adsorption of the molecule, are identified, and their role, as further adsorbate stabilizers, is properly disclosed. The satisfactory agreement with QC data and experiments confirm the reliability of the simulations and the unique opportunity they provide to follow locally molecule adsorption on selected materials

Functional Water Molecules in Rhodopsin Activation

G-protein-coupled receptors (GPCRs) are integral membrane proteins that mediate cellular response to an extensive variety of extracellular stimuli. Studies of rhodopsin, a prototype GPCR, have suggested that water plays an important role in mediating the activation of family A GPCRs. However, our understanding of the function of water molecules in the GPCR activation is still rather limited because resolving the functional water molecules solely based on the results from existing experiments is challenging. Using all-atom molecular dynamics simulations in combination with inhomogeneous fluid theory, we identify in this work the positioning of functional water molecules in the inactive state, the Meta II state, and the constitutive active state of rhodopsin, basing on the thermodynamic signatures of the water molecules. We find that one hydration site likely functions as a switch to regulate the distance between Glu181 and the Schiff base in the rhodopsin activation. We observe that water molecules adjacent to the “NpxxY” motif are not as stable in the Meta II state as in the inactive state as indicated by the thermodynamics signatures, and we rationalize that the behaviors of these water molecules are closely correlated with the rearrangement of the water-mediated hydrogen-bond network in the “NPxxY” motif, which is essential for mediating the activation of the receptor. We thereby propose a hypothesis of the water-mediated rhodopsin activation pathway