Journal of Chemical Physics最新文献

High-resolution techniques capable of manipulating from single molecules to millions of cells are combined with three-dimensional modeling followed by simulation to comprehend the specific aspects of chromosomes. From the theoretical perspective, the energy landscape theory from protein folding inspired the development of the minimal chromatin model (MiChroM). In this work, two biologically relevant MiChroM energy terms were minimized under different conditions, revealing a competition between loci compartmentalization and motor-driven activity mechanisms in chromatin folding. Enhancing the motor activity energy baseline increased the lengthwise compaction and reduced the polymer entanglement. Concomitantly, decreasing compartmentalization-related interactions reduced the overall polymer collapse, although compartmentalization given by the microphase separation remained almost intact. For multiple chromosome simulations, increased motorization intensified the territory formation of the different chains and reduced compartmentalization strength lowered the probability of contact formation of different loci between multiple chains, approximating to the experimental inter-contacts of the human chromosomes. These findings have direct implications for experimental data-driven chromosome modeling, specially those involving multiple chromosomes. The interplay between phase-separation and territory formation mechanisms should be properly implemented in order to recover the genome architecture and dynamics, features that might play critical roles in regulating nuclear functions.

The localization of biomolecular condensates to intracellular membrane surfaces has emerged as an important feature of sub-cellular organization. In this work, we study the wetting behavior of biomolecular condensates on various substrates. We use confocal microscopy to measure the contact angles of model condensates formed by intrinsically disordered protein Ddx4N. We show the importance of taking optical aberrations into account, as these impact apparent contact angle measurements. Ddx4N condensates are seen to partially dry (contact angles above 90°) a model membrane, with little dependence on the magnitude of charge on, or tyrosine content of, Ddx4N. Further contact angle measurements on surfaces of varying hydrophilicity reveal a preference of Ddx4N condensates for hydrophobic surfaces, suggesting an intrinsic repulsion between protein condensates and hydrophilic membrane surfaces. This observation is in line with previous studies relating protein adsorption to surface hydrophilicity. Our work advances the understanding of the molecular details governing the localization of biomolecular condensates.

In light of the recent discrepancies reported between fixed node diffusion Monte Carlo and local natural orbital coupled cluster with single, double, and perturbative triples [CCSD(T)] methodologies for non-covalent interactions in large molecular systems [Al-Hamdani et al., Nat. Commun. 12, 3927 (2021)], the applicability of CCSD(T) is assessed using a model framework. The use of the semi-empirical π-space only Pariser-Parr-Pople (PPP) model for studying large molecules is critically examined and is shown to recover both bandgap closure as system size increases and long range dispersive behavior of r-6 with increasing separation between monomers. Since bandgap closure in systems with long-range Coulomb interactions is problematic for perturbative methods, such as CCSD(T), this model, therefore, serves as a testing ground for such methods, enabling them to be benchmarked with high-order CC methods, which are not possible with ab initio Hamiltonians. Using the PPP model, coupled cluster methodologies, CCSDTQ and CCSDT(Q), are then used to benchmark CCSDT and CCSD(T) methodologies for non-covalent interactions in large one- and two-dimensional molecular systems up to the dibenzocoronene dimer. We show that CCSD(T) demonstrates no signs of overestimating the interaction energy for these systems. Furthermore, by examining the Hartree-Fock HOMO-LUMO gap of these large molecules, the perturbative treatment of the triples contribution in CCSD(T) is not expected to cause problems for accurately capturing the interaction energy for system sizes up to at least circumcoronene.

Understanding the dynamic behavior of complex biomolecules requires simplified models that not only make computations feasible but also reveal fundamental mechanisms. Coarse-graining (CG) achieves this by grouping atoms into beads, whose stochastic dynamics can be derived using the Mori-Zwanzig formalism, capturing both reversible and irreversible interactions. In liquid, the dissipative bead-bead interactions have so far been restricted to hydrodynamic couplings. However, friction does not only arise from the solvent but, notably, from the internal degrees of freedom missing in the CG beads. This leads to an additional "internal friction" whose relevance is studied in this contribution. By comparing with all-atom molecular dynamics (MD), we neatly show that in order to accurately reproduce the dynamics of a globular protein in water using a CG model, not only a precise determination of elastic couplings and the Stokesian self-friction of each bead is required. Critically, the inclusion of internal friction between beads is also necessary for a faithful representation of protein dynamics. We propose to optimize the parameters of the CG model through a self-averaging method that integrates the CG dynamics with an evolution equation for the CG parameters. This approach ensures that selected quantities, such as the radial distribution function and the time correlation of bead velocities, match the corresponding MD values.

The elasticity of phospholipid membranes as a function of hydration was investigated using coarse-grained molecular simulations. Multilamellar membranes consist of two or more lipid bilayers separated by a thin layer of water, a system commonly found in cell membranes that provides surface tension in the alveoli of the lungs and on cartilaginous surfaces of synovial joints. The objective was to quantify the response of such systems to compression in the direction perpendicular to the membranes as a function of the amount of water between the bilayers or hydration of the system. The present study investigated a variety of phospholipids with six levels of hydration found in multilamellar bilayers in biological systems. Our simulations support the existence of a universal behavior of the increase in surface area per lipid as a function of the normal pressure difference, the difference between the pressure applied in the direction normal to the membrane and the pressure applied in the directions parallel to the membrane. Normalizing the surface area per lipid and the pressure difference by their respective values at rupture yields a composite function of two linear regimes for all the hydration levels under investigation. Where possible, a physics-based interpretation of the normalization scales was provided. Although some parameters of the model are determined empirically, the model represents a promising step in continuum modeling of the response of multilamellar lipid membranes as a function of mechanical stress and hydration.

The calculation of the coherent nonlinear response of a system is essential to correctly interpret results from advanced techniques such as two-dimensional coherent spectroscopy. Usually, even for the simplest systems, such calculations are either performed for low-intensity excitations where perturbative methods are valid and/or by assuming a simplified pulse envelope, such as a δ-function in time. Here, we use the phase-cycling method for the exact calculation of the nonlinear response without making the aforementioned approximations even for high-intensity excitation. We compare the simulation results to several experimental observations to prove the validity of these calculations. The saturation of the photon-echo signal from excitons in a semiconductor quantum well sample is measured. The excitation-intensity dependent measurement shows nonlinear contributions up to twelfth order. Intensity-dependent simulations reproduce this effect without explicitly considering higher-order interactions. In addition, we present simulation results that replicate previously reported experiments with high-intensity excitation of semiconductor quantum dots. By accurately reproducing a variety of phenomena such as higher-order contributions, switching of coherent signals, and changes in photon-echo transients, we prove the efficacy of the phase-cycling method to calculate the coherent nonlinear signal for high-intensity excitation. This method would be particularly useful for systems with multiple, well-separated peaks and/or large inhomogeneities.

Molecular dynamics plays a crucial role in understanding molecular interactions, rovibrational coupling mechanisms, and energy transfer processes. Femtosecond time-resolved coherent anti-Stokes Raman scattering spectroscopy was employed to study the molecular dynamics of N2 and O2 in air at room temperature. To reveal hidden spectral features, we have for the first time applied an analytical method that balances time resolution and frequency resolution, namely, the superlet transform (SLT), to perform time-frequency resolved spectral analysis of the complex molecular dynamics of N2 and O2 in air. A distinct evolution of the partial rotational modes of N2 and O2 outside the selective excitation region was observed, which is related to energy transfer collisions between N2 and O2 molecules during the rotational energy relaxation process in air. The SLT results accord well with the S-branch rotational spectra of N2 and O2 obtained from theoretical calculations, confirming the validity of SLT analysis. This method provides a valuable experimental analysis technique to deepen the understanding of the microscopic dynamic processes in molecular dynamics.

In this article, we present our strategy for studying amino-acid sequence dependences on protein structures. For this purpose, performing Metropolis Monte Carlo simulations in the amino-acid sequence space is necessary. We want to use a coarse-grained protein model with an accurate potential energy function. We introduce a method for optimizing potential-energy parameters based on the native protein structure database, Protein Data Bank.

We study disordered networks of coupled bistable elastic elements, representing a coarse-grained view of amorphous solids. We find that such networks self-organize to a marginally stable state, in which the barrier for local activations becomes vanishingly small. The model provides unique access to both local and global properties associated with marginal stability. We directly measure pseudo-gaps in the spectrum of local excitations, as well as diverging fluctuations under shear. Crucially, the dynamics are dominated by a small population of bonds that are locally unstable, which give rise to quasi-localized, low-frequency vibrational modes and scale-free avalanches of instabilities. We propose a correction to the scaling between the pseudo-gap exponent and avalanche statistics based on diverging length fluctuations. Our model combines a coarse-grained view with a continuous, real-space implementation, providing novel insights to a wide class of amorphous solids.