Quantum chemical package Jaguar: A survey of recent developments and unique features.

This paper is dedicated to the quantum chemical package Jaguar, which is commercial software developed and distributed by Schrödinger, Inc. We discuss Jaguar's scientific features that are relevant to chemical research as well as describe those aspects of the program that are pertinent to the user interface, the organization of the computer code, and its maintenance and testing. Among the scientific topics that feature prominently in this paper are the quantum chemical methods grounded in the pseudospectral approach.

Design of Organic Electronic Materials With a Goal-Directed Generative Model Powered by Deep Neural Networks and High-Throughput Molecular Simulations.

In recent years, generative machine learning approaches have attracted significant attention as an enabling approach for designing novel molecular materials with minimal design bias and thereby realizing more directed design for a specific materials property space. Further, data-driven approaches have emerged as a new tool to accelerate the development of novel organic electronic materials for organic light-emitting diode (OLED) applications. We demonstrate and validate a goal-directed generative machine learning framework based on a recurrent neural network (RNN) deep reinforcement learning approach for the design of hole transporting OLED materials.

Molecular-Level Examination of Amorphous Solid Dispersion Dissolution.

Amorphous solid dispersions (ASDs) are commonly used to orally deliver small-molecule drugs that are poorly water-soluble. ASDs consist of drug molecules in the amorphous form which are dispersed in a hydrophilic polymer matrix. Producing a high-performance ASD is critical for effective drug delivery and depends on many factors such as solubility of the drug in the matrix and the rate of drug release in aqueous medium (dissolution), which is linked to bioperformance.

Automated Transition State Search and Its Application to Diverse Types of Organic Reactions.

Transition state search is at the center of multiple types of computational chemical predictions related to mechanistic investigations, reactivity and regioselectivity predictions, and catalyst design. The process of finding transition states in practice is, however, a laborious multistep operation that requires significant user involvement. Here, we report a highly automated workflow designed to locate transition states for a given elementary reaction with minimal setup overhead.

Successful application of the DBLOC method to the hydroxylation of camphor by cytochrome p450.

The activation barrier for the hydroxylation of camphor by cytochrome P450 was computed using a mixed quantum mechanics/molecular mechanics (QM/MM) model of the full protein-ligand system and a fully QM calculation using a cluster model of the active site at the B3LYP/LACVP*/LACV3P** level of theory, which consisted of B3LYP/LACV3P** single point energies computed at B3LYP/LACVP* optimized geometries. From the QM/MM calculation, a barrier height of 17.5 kcal/mol was obtained, while the experimental value was known to be less than or equal to 10 kcal/mol.

Accurate pKa prediction in first-row hexaaqua transition metal complexes using the B3LYP-DBLOC method.

Acid dissociation constants are computed with density functional theory (DFT) for a series of ten first-row octahedral hexaaqua transition metal complexes at the B3LYP/LACV3P** level of theory. These results are then scaled, primarily to correct for basis set effects (as in previous work on predicting pKa's in organic systems1-5). Finally, localized orbital corrections (LOCs), developed by fitting properties such as ionization potentials, electron affinities, and ligand removal energies in prior publications,3,4,6,7 are applied without any further parameter adjustment.

Accurate Force Field Development for Modeling Conjugated Polymers.

The modeling of the conformational properties of conjugated polymers entails a unique challenge for classical force fields. Conjugation imposes strong constraints upon bond rotation. Planar configurations are favored, but the concomitantly shortened bond lengths result in moieties being brought into closer proximity than usual.

Realistic cluster modeling of electron transport and trapping in solvated TiO2 nanoparticles.

We have developed a cluster model of a TiO(2) nanoparticle in the dye-sensitized solar cell and used first-principles quantum chemistry, coupled with a continuum solvation model, to compute structures and energetics of key electronic and structural intermediates and transition states. Our results suggest the existence of shallow surface trapping states induced by small cations and continuum solvent effect as well as the possibility of the existence of a surface band which is 0.3-0.

A B3LYP-DBLOC empirical correction scheme for ligand removal enthalpies of transition metal complexes: parameterization against experimental and CCSD(T)-F12 heats of formation.

Average ligand removal enthalpies of 30 differently coordinated mono-nuclear fourth-row transition metal complexes taken from a database recently considered by Johnson and Becke [Can. J. Chem.

Development of Accurate DFT Methods for Computing Redox Potentials of Transition Metal Complexes: Results for Model Complexes and Application to Cytochrome P450.

Single-electron reduction half potentials of 95 octahedral fourth-row transition metal complexes binding a diverse set of ligands have been calculated at the unrestricted pseudospectral B3LYP/LACV3P level of theory in a continuum solvent. Through systematic comparison of experimental and calculated potentials, it is determined that B3LYP strongly overbinds the d-manifold when the metal coordinates strongly interacting ligands and strongly underbinds the d-manifold when the metal coordinates weakly interacting ligands. These error patterns give rise to an extension of the localized orbital correction (LOC) scheme previously developed for organic molecules and which was recently extended to the spin-splitting properties of organometallic complexes.

Systematic investigation of the catalytic cycle of a single site ruthenium oxygen evolving complex using density functional theory.

The mechanism of water oxidation by a single site ruthenium oxygen evolving complex is investigated using fully unrestricted pseudospectral B3LYP with the effective core potential LACV3P in continuum solvent with some quantum mechanical waters. Guess wave functions have been used that allow greater flexibility in sampling different electronic configurations of the complex. Systematic comparison with experiment is improved using these guesses because they provide a complete analysis of the low energy manifold and help to alleviate the formal disconnect between theory and experiment in assigning Lewis structures for transition metal complexes.

Correcting Systematic Errors in DFT Spin-Splitting Energetics for Transition Metal Complexes.

Spin-splittings of 57 octahedral first-row transition metal complexes calculated with B3LYP are compared with a database of experimental spectra collected from the literature. A variety of transition metal centers in various oxidation states and multiplicities along with a number of different coordinating ligands are considered. Environmental effects have been included to enable reasonable quantitative comparison with experiment.

Transferability in the natural linear-scaled coupled-cluster effective Hamiltonian approach: Applications to dynamic polarizabilities and dispersion coefficients.

A natural linear-scaled coupled-cluster (CC) method has been developed to calculate the response properties of large molecules, for example, dynamic polarizabilities and dispersion coefficients. The method is based on the transferability of the CC effective Hamiltonian from the equation-of-motion (EOM)-CC methods, subject to its representation in terms of highly transferable natural localized molecular orbitals. This transferability allows the interactions among regions in a molecule to be classified according to their important inter-region excitations and de-excitations.

Natural linear-scaled coupled-cluster theory with local transferable triple excitations: applications to peptides.

The natural linear-scaled coupled-cluster (NLSCC) method ( Flocke, N.; Bartlett, R. J.

Inhibitors tethered near the acetylcholinesterase active site serve as molecular rulers of the peripheral and acylation sites.

The acetylcholinesterase (AChE) active site consists of a narrow gorge with two separate ligand binding sites: an acylation site (or A-site) at the bottom of the gorge where substrate hydrolysis occurs and a peripheral site (or P-site) at the gorge mouth. AChE is inactivated by organophosphates as they pass through the P-site and phosphorylate the catalytic serine in the A-site. One strategy to protect against organophosphate inactivation is to design cyclic ligands that will bind specifically to the P-site and block the passage of organophosphates but not acetylcholine.