Maynardpruitt7475

Ectodomain-only simulations with benzene exhibited unfolding effects not observed in the more physiologically relevant membrane-associated systems. A cryptic pocket which has been experimentally shown to bind n-octyl-β-d-glucoside detergent was consistently revealed in all benzene-containing simulations. The addition of benzene also enhanced the flexibility and hydrophobic exposure of cryptic pockets at a key, functional interface in the E protein and revealed a novel, potentially druggable pocket that may be targeted to prevent conformational changes associated with viral entry into the cell.We report on first-principles quantum-dynamical and quantum-classical simulations of photoinduced exciton dynamics in oligothiophene chain segments, representative of intrachain exciton migration in the poly(3-hexylthiophene) (P3HT) polymer. Following up on our recent study (Binder R.; Burghardt, I. Faraday Discuss.2020, 221, 406), multilayer multiconfiguration time-dependent Hartree calculations for a short oligothiophene segment comprising 20 monomer units (OT-20) are carried out to obtain full quantum-dynamical simulations at finite temperature. These are employed to benchmark mean-field Ehrenfest calculations, which are shown to give qualitatively correct results for the present system. Periodic boundary conditions turn out to significantly improve earlier estimates of diffusion coefficients. Using the Ehrenfest approach, a series of calculations are subsequently carried out for larger lattices (OT-40 to OT-80), leading to estimates for temperature-dependent mean-squared displacements, which are found to exhibit a near-linear dependence as a function of time. The resulting diffusion coefficient estimates are an increasing function of temperature, whose detailed functional form depends on the degree of static disorder. With a realistic static disorder parameter (σs ≃ 0.06 eV), the diffusion coefficients decrease from D ∼ 1 × 10-2 cm2 s-1 to D ∼ 1 × 10-3 cm2 s-1, in qualitative agreement with experimental data for P3HT. The dynamical scenario obtained from our simulations shows that exciton migration in P3HT-type chains is a largely adiabatic process throughout the temperature regime we investigated (i.e., T = 50-300 K). buy UNC2250 resulting picture of exciton migration is a coherent, but not bandlike, motion of an exciton-polaron driven by fluctuations induced by low-frequency modes. This process acquires partial hopping character if static disorder becomes prominent and Anderson localization sets in.Can current simulations quantitatively predict the stability of ribonucleic acids (RNAs)? In this research, we apply a free-energy perturbation simulation of RNAs containing inosine, a modified ribonucleic base, to the derivation of RNA nearest-neighbor parameters. A parameter set derived solely from 30 simulations was used to predict the free-energy difference of the RNA duplex with a mean unbiased error of 0.70 kcal/mol, which is a level of accuracy comparable to that obtained with parameters derived from 25 experiments. We further show that the error can be lowered to 0.60 kcal/mol by combining the simulation-derived free-energy differences with experimentally measured differences. #link# This protocol can be used as a versatile method for deriving nearest-neighbor parameters of RNAs with various modified bases.Analytical gradient theory for the second-order extended multiconfiguration quasi-degenerate perturbation theory (XMCQDPT2), which can be regarded as the multistate version of the multireference second-order Møller-Plesset perturbation theory (MRMP2), is formulated and implemented. The theory is similar to the previous analytical gradient theory for MCQDPT2, but we take into account the intruder state avoidance (ISA) technique and the "extension" of the MCQDPT2 theory by Granovsky. Although the (X)MCQDPT2 theory is not invariant with respect to rotations among the active orbitals, the resulting analytical gradients are accurate. We demonstrate the utility of the current algorithm in optimizing the minimum energy conical intersections (MECIs) of ethylene, butadiene, benzene, the retinal model chromophore PSB3, and the green fluorescent protein model chromophore pHBI. The XMCQDPT2 MECIs are very similar to the XMS-CASPT2 MECIs in terms of molecular conformation and the computed energies. We also discuss possible improvements of the current algorithm.Quadrupolar NMR relaxation rates were computed for aqueous 133Cs+, 131Xe, and 127I- via Kohn-Sham (KS) density functional theory-based ab initio molecular dynamics and KS calculations of the electric field gradient (EFG) tensors along the trajectories. The resulting rates are within a factor of 1-3 of the experimental values and can be compared to available results from classical dynamics and EFGs from electrostatic models with corrections via Sternheimer antishielding factors. Relativistic effects are shown to have an enhancing effect on the magnitude of the EFGs. An analysis of the EFGs was carried out in terms of localized molecular orbitals to elucidate contributions from the solvent versus solute polarization and assess the validity of the Sternheimer approximation for these systems.Herein, we detail an approach to accelerate the computational screening of materials for properties dictated by the kinetics of solid-state diffusion through reliably and rapidly identifying upper and lower bounds to the transition state (TS) energy through our proposed modified single iteration synchronous-transit (MSIST) approach. While this sacrifices providing detailed information of the explicit TS structure, it requires only 30% of the force evaluations of a full nudged elastic band (NEB) TS search and reduces the computational demand to compute estimated diffusion barriers by ∼70% on average. In all 53 cases in which we explicitly compared our results to those of an NEB calculation, the upper and lower bounds identified using this approach bracketed the TS energy calculated with explicit NEB calculations. We use the applications of diffusion of Na+ in potential sodium-ion battery electrodes and oxygen vacancy diffusion in solid-oxide fuel cell electrodes and redox mediators for solar thermochemical hydted regression techniques. MSIST enables the analysis of the kinetics of solid-state diffusion across larger sets of materials and can thus efficiently provide data to train statistically learned models of diffusion and to develop physical insights into the diffusion process.The study of photoinduced dynamics in chemical systems necessitates accurate and computationally efficient electronic structure methods, especially as the systems of interest grow larger. The linear response hole-hole Tamm-Dancoff approximated (hh-TDA) density functional theory method was recently proposed to satisfy such demands. The N-electron electronic states are obtained by means of double annihilations on a doubly anionic (N + 2)-electron reference state, allowing for the ground and excited states to be formed on the same footing and thus enabling the correct description of conical intersections. Dynamic electron correlation effects are incorporated by means of the exchange-correlation functional. The accuracy afforded by the simultaneous treatment of static and dynamic correlation in addition to the relatively low computational cost, comparable to that of time-dependent density functional theory (TDDFT), makes it a promising ab initio electronic structure method for on-the-fly generation of potential ere. FOMO-hh-TDA-BHLYP faithfully reproduces the nonadiabatic dynamics of trans-azobenzene (TAB) and is used to characterize the excited state decay pathways from the first (nπ*) excited state.Full configuration interaction (FCI) solvers are limited to small basis sets due to their expensive computational costs. link2 An optimal orbital selection for FCI (OptOrbFCI) is proposed to boost the power of existing FCI solvers to pursue the basis set limit under a computational budget. The optimization problem coincides with that of the complete active space SCF method (CASSCF), while OptOrbFCI is algorithmically quite different. OptOrbFCI effectively finds an optimal rotation matrix via solving a constrained optimization problem directly to compress the orbitals of large basis sets to one with a manageable size, conducts FCI calculations only on rotated orbital sets, and produces a variational ground-state energy and its wave function. Coupled with coordinate descent full configuration interaction (CDFCI), we demonstrate the efficiency and accuracy of the method on the carbon dimer and nitrogen dimer under basis sets up to cc-pV5Z. We also benchmark the binding curve of the nitrogen dimer under the cc-pVQZ basis set with 28 selected orbitals, which provide consistently lower ground-state energies than the FCI results under the cc-pVDZ basis set. The dissociation energy in this case is found to be of higher accuracy.Modern high-throughput structure-based drug discovery algorithms consider ligand flexibility, but typically with low accuracy, which results in a loss of performance in the derived models. Here we present the bioactive conformational ensemble (BCE) server and its associated database. The server creates conformational ensembles of drug-like ligands and stores them in the BCE database, where a variety of analyses are offered to the user. The workflow implemented in the BCE server combines enhanced sampling molecular dynamics with self-consistent reaction field quantum mechanics (SCRF/QM) calculations. The server automatizes all of the steps to transform one-dimensional (1D) or 2D representation of drugs into 3D molecules, which are then titrated, parametrized, hydrated, and optimized before being subjected to Hamiltonian replica-exchange (HREX) molecular dynamics simulations. Ensembles are collected and subjected to a clustering procedure to derive representative conformers, which are then analyzed at the SCRF/QM level of theory. All structural data are organized in a noSQL database accessible through a graphical interface and in a programmatic manner through a REST API. The server allows the user to define a private workspace and offers a deposition protocol as well as input files for "in house" calculations in those cases where confidentiality is a must. The database and the associated server are available at https//mmb.irbbarcelona.org/BCE.Hybrid quantum mechanical and molecular mechanical (QM/MM) approaches facilitate computational modeling of large biological and materials systems. link3 Typically, in QM/MM, a small region of the system is modeled with an accurate quantum mechanical method and its surroundings with a more efficient alternative, such as a classical force field or the effective fragment potential (EFP). The reliability of QM/MM calculations depends largely on the treatment of interactions between the two subregions, also known as embedding. The polarizable embedding, which allows mutual polarization between solvent and solute, is considered to be essential for describing electronic excitations in polar solvents. In this work, we employ the QM/EFP model and extend the polarizable embedding by incorporating two short-range terms-a charge penetration correction to the electrostatic term and the exchange-repulsion term-both of which are modeled with one-electron contributions to the quantum Hamiltonian. We evaluate the accuracy of these terms by computing excitation energies across 37 molecular clusters consisting of biologically relevant chromophores surrounded by polar solvent molecules.