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.

Large Computational Survey of Intrinsic Reactivity of Aromatic Carbon Atoms with Respect to a Model Aldehyde Oxidase.

Aldehyde oxidase (AOX) and other related molybdenum-containing enzymes are known to oxidize the C-H bonds of aromatic rings. This process contributes to the metabolism of pharmaceutical compounds and, therefore, is of vital importance to drug pharmacokinetics. The present work describes an automated computational workflow and its use for the prediction of intrinsic reactivity of small aromatic molecules toward a minimal model of the active site of AOX.

Pattern-free generation and quantum mechanical scoring of ring-chain tautomers.

In contrast to the computational generation of conventional tautomers, the analogous operation that would produce ring-chain tautomers is rarely available in cheminformatics codes. This is partly due to the perceived unimportance of ring-chain tautomerism and partly because specialized algorithms are required to realize the non-local proton transfers that occur during ring-chain rearrangement. Nevertheless, for some types of organic compounds, including sugars, warfarin analogs, fluorescein dyes and some drug-like compounds, ring-chain tautomerism cannot be ignored.

Accurate Quantum Chemical Calculation of Ionization Potentials: Validation of the DFT-LOC Approach via a Large Data Set Obtained from Experiments and Benchmark Quantum Chemical Calculations.

Density functional theory (DFT) is known to often fail when calculating thermodynamic values, such as ionization potentials (IPs), due to nondynamical error (i.e., the self-interaction term).

Generation of Tautomers Using Micro-p K's.

Solutions of organic molecules containing one or more heterocycles with conjugated bonds may exist as a mixture of tautomers, but typically only a few of them are significantly populated even though the potential number grows combinatorially with the number of protonation and deprotonation sites. Generating the most stable tautomers from a given input structure is an important and challenging task, and numerous algorithms to tackle it have been proposed in the literature. This work describes a novel approach for tautomer prediction that involves the combined use of molecular mechanics, semiempirical quantum chemistry, and density functional theory.

Empirical Conversion of p Values between Different Solvents and Interpretation of the Parameters: Application to Water, Acetonitrile, Dimethyl Sulfoxide, and Methanol.

An empirical conversion method (ECM) that transforms p values of arbitrary organic compounds from one solvent to the other is introduced. We demonstrate the method's usefulness and performance on p conversions involving water and organic solvents acetonitrile (MeCN), dimethyl sulfoxide (MeSO), and methanol (MeOH). We focus on the p conversion from the known reference value in water to the other three organic solvents, although such a conversion can also be performed between any pair of the considered solvents.

Weighted Averaging Scheme and Local Atomic Descriptor for pK Prediction Based on Density Functional Theory.

As a continuation of our work on developing a density functional theory-based pK predictor, we present conceptual improvements to our previously published shell model, which is a hierarchical organization of pK training sets and which, in principle, covers all chemical space. The improvements concern the way the studied chemical compound is associated with the data points from the training sets. By introducing a new descriptor of the local atomic environment which foregoes dependence on chemical bonding and connectivity, we are able to automatically locate molecules from the training set that are most relevant to the proton dissociation equilibrium under study.

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.

Multiconformation, Density Functional Theory-Based pK Prediction in Application to Large, Flexible Organic Molecules with Diverse Functional Groups.

We consider the conformational flexibility of molecules and its implications for micro- and macro-pK. The corresponding formulas are derived and discussed against the background of a comprehensive scientific and algorithmic description of the latest version of our computer program Jaguar pK, a density functional theory-based pK predictor, which is now capable of acting on multiple conformations explicitly. Jaguar pK is essentially a complex computational workflow incorporating research and technologies from the fields of cheminformatics, molecular mechanics, quantum mechanics, and implicit solvation models.