Large-Z atoms in the strong-interaction limit of DFT: Implications for gradient expansions and for the Lieb-Oxford bound.

We numerically study the strong-interaction limit of the exchange-correlation functional for neutral atoms and Bohr atoms as the number of electrons increases. Using a compact representation, we analyze the second-order gradient expansion, comparing it with the one for exchange (weak interaction limit). The two gradient expansions, at strong and weak interaction, turn out to be very similar in magnitude but with opposite signs.

Regularized and Opposite Spin-Scaled Functionals from Møller-Plesset Adiabatic Connection─Higher Accuracy at Lower Cost.

Noncovalent interactions (NCIs) play a crucial role in biology, chemistry, material science, and everything in between. To improve pure quantum-chemical simulations of NCIs, we propose a methodology for constructing approximate correlation energies by combining an interpolation along the Møller-Plesset adiabatic connection (MP AC) with a regularization and spin-scaling strategy applied to MP2 correlation energies. This combination yields κ-SPL2, which exhibits superior accuracy for NCIs compared to any of the individual strategies.

Electronic Excited States in Extreme Limits via Ensemble Density Functionals.

Density functional theory (DFT) has greatly expanded our ability to affordably compute and understand electronic ground states, by replacing intractable ab initio calculations by models based on paradigmatic physics from high- and low-density limits. But, a comparable treatment of excited states lags behind. Here, we solve this outstanding problem by employing a generalization of density functional theory to ensemble states (EDFT).

Gradient Expansions for the Large-Coupling Strength Limit of the Møller-Plesset Adiabatic Connection.

The adiabatic connection that has, as weak-interaction expansion, the Møller-Plesset perturbation series has been recently shown to have a large coupling-strength expansion, in terms of functionals of the Hartree-Fock density with a clear physical meaning. In this work, we accurately evaluate these density functionals and we extract second-order gradient coefficients from the data for neutral atoms, following ideas similar to the ones used in the literature for exchange, with some modifications. These new gradient expansions will be the key ingredient for performing interpolations that have already been shown to reduce dramatically MP2 errors for large noncovalent complexes.

Dispersion without Many-Body Density Distortion: Assessment on Atoms and Small Molecules.

The "fixed diagonal matrices" (FDM) dispersion formalism [Kooi, D. P.; et al.

Large coupling-strength expansion of the Møller-Plesset adiabatic connection: From paradigmatic cases to variational expressions for the leading terms.

We study in detail the first three leading terms of the large coupling-strength limit of the adiabatic connection that has as weak-interaction expansion the Møller-Plesset perturbation theory. We first focus on the H atom, both in the spin-polarized and the spin-unpolarized cases, reporting numerical and analytical results. In particular, we derive an asymptotic equation that turns out to have simple analytical solutions for certain channels.

London dispersion forces without density distortion: a path to first principles inclusion in density functional theory.

We analyse a path to construct density functionals for the dispersion interaction energy from an expression in terms of the ground state densities and exchange-correlation holes of the isolated fragments. The expression is based on a constrained search formalism for a supramolecular wavefunction that is forced to leave the diagonal of the many-body density matrix of each fragment unchanged, and is exact for the interaction between one-electron densities. We discuss several aspects: the necessary features of a density functional approximation for the exchange-correlation holes of the monomers, the optimal choice of the one-electron basis (named "dispersals"), and the functional derivative with respect to monomer density variations.

A Variational Approach to London Dispersion Interactions without Density Distortion.

We introduce a class of variational wave functions that captures the long-range interaction between neutral systems (atoms and molecules) without changing the diagonal of the density matrix of each monomer. The corresponding energy optimization yields explicit expressions for the dispersion coefficients in terms of the ground-state pair densities of the isolated systems, providing a clean theoretical framework to build new approximations in several contexts. As the individual monomer densities are kept fixed, we can also unambiguously assess the effect of the density distortion on London dispersion interactions; for example, we obtain virtually exact dispersion coefficients between two hydrogen atoms up to C and relative errors below 0.

Local and global interpolations along the adiabatic connection of DFT: a study at different correlation regimes.

Interpolating the exchange-correlation energy along the density-fixed adiabatic connection of density functional theory is a promising way to build approximations that are not biased toward the weakly correlated regime. These interpolations can be performed at the global (integrated over all spaces) or at the local level, using energy densities. Many features of the relevant energy densities as well as several different ways to construct these interpolations, including comparisons between global and local variants, are investigated here for the analytically solvable Hooke's atom series, which allows for an exploration of different correlation regimes.

eTOX ALLIES: an automated pipeLine for linear interaction energy-based simulations.

Background: Computational methods to predict binding affinities of small ligands toward relevant biological (off-)targets are helpful in prioritizing the screening and synthesis of new drug candidates, thereby speeding up the drug discovery process. However, use of ligand-based approaches can lead to erroneous predictions when structural and dynamic features of the target substantially affect ligand binding. Free energy methods for affinity computation can include steric and electrostatic protein-ligand interactions, solvent effects, and thermal fluctuations, but often they are computationally demanding and require a high level of supervision.

Fermionic Statistics in the Strongly Correlated Limit of Density Functional Theory.

Exact pieces of information on the adiabatic connection integrand, W[ρ], which allows evaluation of the exchange-correlation energy of Kohn-Sham density functional theory, can be extracted from the leading terms in the strong coupling limit (λ → ∞, where λ is the strength of the electron-electron interaction). In this work, we first compare the theoretical prediction for the two leading terms in the strong coupling limit with data obtained via numerical implementation of the exact Levy functional in the simple case of two electrons confined in one dimension, confirming the asymptotic exactness of these two terms. We then carry out a first study on the incorporation of the Fermionic statistics at large coupling λ, both numerical and theoretical, confirming that spin effects enter at orders ∼e.

Improving the iterative Linear Interaction Energy approach using automated recognition of configurational transitions.

Recently an iterative method was proposed to enhance the accuracy and efficiency of ligand-protein binding affinity prediction through linear interaction energy (LIE) theory. For ligand binding to flexible Cytochrome P450s (CYPs), this method was shown to decrease the root-mean-square error and standard deviation of error prediction by combining interaction energies of simulations starting from different conformations. Thereby, different parts of protein-ligand conformational space are sampled in parallel simulations.

Integrative Modeling Strategies for Predicting Drug Toxicities at the eTOX Project.

Early prediction of safety issues in drug development is at the same time highly desirable and highly challenging. Recent advances emphasize the importance of understanding the whole chain of causal events leading to observable toxic outcomes. Here we describe an integrative modeling strategy based on these ideas that guided the design of eTOXsys, the prediction system used by the eTOX project.