Top-Down versus Bottom-Up Approaches for σ-Functionals Based on the Approximate Exchange Kernel.

Recently, we investigated a number of so-called σ- and τ-functionals based on the adiabatic-connection fluctuation-dissipation theorem (ACFDT); particularly, extensions of the random phase approximation (RPA) with inclusion of an exchange kernel in the form of an antisymmetrized Hartree kernel. One of these functionals, based upon the approximate exchange kernel (AXK) of Bates and Furche, leads to a nonlinear contribution of the spline function used within σ-functionals, which we previously avoided through the introduction of a simplified "top-down" approach in which the σ-functional modification is inserted a posteriori following the analytic coupling strength integration within the framework of the ACFDT and which was shown to provide excellent performance for the GMTKN55 database when using hybrid PBE0 reference orbitals. In this work, we examine the analytic "bottom-up" approach in which the spline function is inserted a priori, i.

A Constraint-Based Orbital-Optimized Excited State Method (COOX).

In this work, we present a novel method to directly calculate targeted electronic excited states within a self-consistent field calculation based on constrained density functional theory (cDFT). The constraint is constructed from the static occupied-occupied and virtual-virtual parts of the excited state difference density from (simplified) linear-response time-dependent density functional theory calculations (LR-TDDFT). Our new method shows a stable convergence behavior, provides an accurate excited state density adhering to the Aufbau principle, and can be solved within a restricted SCF for singlet excitations to avoid spin contamination.

Low-Scaling, Efficient and Memory Optimized Computation of Nuclear Magnetic Resonance Shieldings within the Random Phase Approximation Using Cholesky-Decomposed Densities and an Attenuated Coulomb Metric.

An efficient method for the computation of nuclear magnetic resonance (NMR) shielding tensors within the random phase approximation (RPA) is presented based on our recently introduced resolution-of-the-identity (RI) atomic orbital RPA NMR method [Drontschenko, V. 2023, 19, 7542-7554] utilizing Cholesky decomposed density type matrices and employing an attenuated Coulomb RI metric. The introduced sparsity is efficiently exploited using sparse matrix algebra.

Simulation of the non-adiabatic dynamics of an enone-Lewis acid complex in an explicit solvent.

Unlocking the full potential of Lewis acid catalysis for photochemical transformations requires a comprehensive understanding of the ultrafast dynamics of substrate-Lewis acid complexes. In a previous article [Peschel , 2021, , 10155], time-resolved spectroscopy supported by static calculations revealed that the Lewis acid remains attached during the relaxation of the model complex cyclohexenone-BF. In contrast to the experimental observation, surface-hopping dynamics in the gas phase predicted ultrafast heterolytic dissociation.

Accurate NMR Shieldings with σ-Functionals.

In recent years, density-functional methods relying on a new type of fifth-rung correlation functionals called σ-functionals have been introduced. σ-Functionals are technically closely related to the random phase approximation and require the same computational effort but yield distinctively higher accuracies for reaction and transition state energies of main group chemistry and even outperform double-hybrid functionals for these energies. In this work, we systematically investigate how accurate σ-functionals can describe nuclear magnetic resonance (NMR) shieldings.

QM/MM Free Energy Calculations of Long-Range Biological Protonation Dynamics by Adaptive and Focused Sampling.

Water-mediated proton transfer reactions are central for catalytic processes in a wide range of biochemical systems, ranging from biological energy conversion to chemical transformations in the metabolism. Yet, the accurate computational treatment of such complex biochemical reactions is highly challenging and requires the application of multiscale methods, in particular hybrid quantum/classical (QM/MM) approaches combined with free energy simulations. Here, we combine the unique exploration power of new advanced sampling methods with density functional theory (DFT)-based QM/MM free energy methods for multiscale simulations of long-range protonation dynamics in biological systems.

Efficient Exploitation of Numerical Quadrature with Distance-Dependent Integral Screening in Explicitly Correlated F12 Theory: Linear Scaling Evaluation of the Most Expensive RI-MP2-F12 Term.

We present a linear scaling atomic orbital based algorithm for the computation of the most expensive exchange-type RI-MP2-F12 term by employing numerical quadrature in combination with CABS-RI to avoid six-center-three-electron integrals. Furthermore, a robust distance-dependent integral screening scheme, based on integral partition bounds [Thompson, T. H.

Systematic QM/MM Study for Predicting P NMR Chemical Shifts of Adenosine Nucleotides in Solution and Stages of ATP Hydrolysis in a Protein Environment.

NMR (nuclear magnetic resonance) spectroscopy allows for important atomistic insights into the structure and dynamics of biological macromolecules; however, reliable assignments of experimental spectra are often difficult. Herein, quantum mechanical/molecular mechanical (QM/MM) calculations can provide crucial support. A major problem for the simulations is that experimental NMR signals are time-averaged over much longer time scales, and since computed chemical shifts are highly sensitive to local changes in the electronic and structural environment, sufficiently large averages over representative structural ensembles are essential.

Exploring Chemical Space Using Hyperreactor Dynamics.

In recent years, first-principles exploration of chemical reaction space has provided valuable insights into intricate reaction networks. Here, we introduce hyperreactor dynamics, which enables rapid screening of the accessible chemical space from a given set of initial molecular species, predicting new synthetic routes that can potentially guide subsequent experimental studies. For this purpose, different hyperdynamics derived bias potentials are applied along with pressure-inducing spherical confinement of the molecular system in molecular dynamics simulations to efficiently enhance reactivity under mild conditions.

Improved Sampling of Adaptive Path Collective Variables by Stabilized Extended-System Dynamics.

Because of the complicated multistep nature of many biocatalytic reactions, an a priori definition of reaction coordinates is difficult. Therefore, we apply enhanced sampling algorithms along with adaptive path collective variables (PCVs), which converge to the minimum free energy path (MFEP) during the simulation. We show how PCVs can be combined with the highly efficient well-tempered metadynamics extended-system adaptive biasing force (WTM-eABF) hybrid sampling algorithm, offering dramatically increased sampling efficiency due to its fast adaptation to path updates.

Highly accurate σ- and τ-functionals for beyond-RPA methods with approximate exchange kernels.

σ-Functionals are promising new developments for the Kohn-Sham correlation energy based upon the direct Random Phase Approximation (dRPA) within the adiabatic connection formalism, providing impressive improvements over dRPA for a broad range of benchmarks. However, σ-functionals exhibit a high amount of self-interaction inherited from the approximations made within dRPA. Inclusion of an exchange kernel in deriving the coupling-strength-dependent density-density response function leads to so-called τ-functionals, which - apart from a fourth-order Taylor series expansion - have only been realized in an approximate fashion so far to the best of our knowledge, most notably in the form of scaled σ-functionals.

Analytical Second-Order Properties for the Random Phase Approximation: Nuclear Magnetic Resonance Shieldings.

A method for the analytical computation of nuclear magnetic resonance (NMR) shieldings within the direct random phase approximation (RPA) is presented. As a starting point, we use the RPA ground-state energy expression within the resolution-of-the-identity approximation in the atomic-orbital formalism. As has been shown in a recent benchmark study using numerical second derivatives [Glasbrenner, M.

Postsynthetic Transformation of Imine- into Nitrone-Linked Covalent Organic Frameworks for Atmospheric Water Harvesting at Decreased Humidity.

Herein, we report a facile postsynthetic linkage conversion method giving synthetic access to nitrone-linked covalent organic frameworks (COFs) from imine- and amine-linked COFs. The new two-dimensional (2D) nitrone-linked covalent organic frameworks, NO-PI-3-COF and NO-TTI-COF, are obtained with high crystallinity and large surface areas. Nitrone-modified pore channels induce condensation of water vapor at 20% lower humidity compared to their amine- or imine-linked precursor COFs.

Scaled opposite-spin atomic-orbital based algebraic diagrammatic construction scheme for the polarization propagator with asymptotic linear-scaling effort: Theory and implementation.

A novel local approach for the quantum-chemical computation of excited states is presented, where the concept of the atomic-orbital formulation of the second-order Møller-Plesset energy expression is extended to the second-order algebraic diagrammatic construction scheme by virtue of the Laplace transform. The scaled opposite-spin second-order algebraic diagrammatic construction method with Cholesky decomposed densities and density-fitting, or CDD-DF-SOS-ADC(2) for short, exploits the sparsity of the two-electron repulsion integrals, the atomic ground-state density matrix, and the atomic transition density matrix to drastically reduce the computational effort. By using a local density-fitting approximation, it is shown that asymptotically linear scaling can be achieved for linear carboxylic acids.

Efficient Method for the Computation of Frozen-Core Nuclear Gradients within the Random Phase Approximation.

A method for the evaluation of analytical frozen-core gradients within the random phase approximation is presented. We outline an efficient way to evaluate the response of the density of active electrons arising only when introducing the frozen-core approximation and constituting the main difficulty, together with the response of the standard Kohn-Sham density. The general framework allows to extend the outlined procedure to related electron correlation methods in the atomic orbital basis that require the evaluation of density responses, such as second-order Møller-Plesset perturbation theory or coupled cluster variants.

Fully Automated Generation of Prebiotically Relevant Reaction Networks from Optimized Nanoreactor Simulations.

The nanoreactor approach first introduced by the group of Martı́nez [Wang et al. 1044-1048] has recently attracted much attention because of its ability to accelerate the discovery of reaction pathways. Here, we provide a comprehensive study of various simulation parameters and present an alternative implementation for the reactivity-enhancing spherical constraint function, as well as for the detection of reaction events.

Targeted Mutagenesis of the Multicopy Gene Family in Allotetraploid Reduces Pungency in Fresh Leaves across Environments.

Recent breeding efforts in have focused on the development of new oilseed feedstock crop for biofuels (e.g., ethanol, biodiesel, bio-jet fuel), bio-industrial uses (e.

Accelerating Hybrid Density Functional Theory Molecular Dynamics Simulations by Seminumerical Integration, Resolution-of-the-Identity Approximation, and Graphics Processing Units.

The computationally very demanding evaluation of the 4-center-2-electron (4c2e) integrals and their respective integral derivatives typically represents the major bottleneck within hybrid Kohn-Sham density functional theory molecular dynamics simulations. Building upon our previous works on seminumerical exact-exchange (sn-LinK) [Laqua, H., Thompsons, T.

An effective sub-quadratic scaling atomic-orbital reformulation of the scaled opposite-spin RI-CC2 ground-state model using Cholesky-decomposed densities and an attenuated Coulomb metric.

An atomic-orbital reformulation of the Laplace-transformed scaled opposite-spin (SOS) coupled cluster singles and doubles (CC2) model within the resolution of the identity (RI) approximation (SOS-RI-CC2) is presented that extends its applicability to molecules with several hundreds of atoms and triple-zeta basis sets. We exploit sparse linear algebra and an attenuated Coulomb metric to decrease the disk space demands and the computational efforts. In this way, an effective sub-quadratic computational scaling is achieved with our ω-SOS-CDD-RI-CC2 model.

From free-energy profiles to activation free energies.

Given a chemical reaction going from reactant (R) to the product (P) on a potential energy surface (PES) and a collective variable (CV) discriminating between R and P, we define the free-energy profile (FEP) as the logarithm of the marginal Boltzmann distribution of the CV. This FEP is not a true free energy. Nevertheless, it is common to treat the FEP as the "free-energy" analog of the minimum potential energy path and to take the activation free energy, ΔF , as the difference between the maximum at the transition state and the minimum at R.

Tensor-Hypercontracted MP2 First Derivatives: Runtime and Memory Efficient Computation of Hyperfine Coupling Constants.

We employ our recently introduced tensor-hypercontracted (THC) second-order Møller-Plesset perturbation theory (MP2) method [Bangerter, F. H., Glasbrenner, M.

Development of hetero-triaryls as a new chemotype for subtype-selective and potent Sirt5 inhibition.

In contrast to other sirtuins (NAD-dependent class III lysine deacylases), inhibition of Sirt5 is poorly investigated, yet. Our present work is based on the recently identified Sirt5 inhibitor balsalazide, an approved drug with negligible bioavailability after oral administration. After gaining first insights into its structure-activity relationship in previous work, we were able to now develop heteroaryl-triaryls as a novel chemotype of drug-like, potent and subtype-selective Sirt5 inhibitors.

Statistically optimal analysis of the extended-system adaptive biasing force (eABF) method.

The extended-system adaptive biasing force (eABF) method and its newer variants offer rapid exploration of the configuration space of chemical systems. Instead of directly applying the ABF bias to collective variables, they are harmonically coupled to fictitious particles, which separates the problem of enhanced sampling from that of free energy estimation. The prevalent analysis method to obtain the potential of mean force (PMF) from eABF is thermodynamic integration.

Efficient Integral-Direct Methods for Self-Consistent Reduced Density Matrix Functional Theory Calculations on Central and Graphics Processing Units.

Reduced density matrix functional theory (RDMFT), a promising direction in the problem of describing strongly correlated systems, is currently limited by its explicit dependence on natural orbitals and, by extension, the costly need to construct two-electron integrals in the molecular orbital basis. While a resolution-of-the-identity approach can reduce the asymptotic scaling behavior from () to (), this is still prohibitively expensive for large systems, especially considering the usually slow convergence and the resulting high number of orbital optimization steps. In this work, efficient integral-direct methods are derived and benchmarked for various approximate functionals.