Design of SARS-CoV-2 Main Protease Inhibitors Using Artificial Intelligence and Molecular Dynamic Simulations.

Drug design is a time-consuming and cumbersome process due to the vast search space of drug-like molecules and the difficulty of investigating atomic and electronic interactions. The present paper proposes a computational drug design workflow that combines artificial intelligence (AI) methods, i.e., an evolutionary algorithm and artificial neural network model, and molecular dynamics (MD) simulations to design and evaluate potential drug candidates. For the purpose of illustration, the proposed workflow was applied to design drug candidates against the main protease of severe acute respiratory syndrome coronavirus 2. From the ∼140,000 molecules designed using AI methods, MD analysis identified two molecules as potential drug candidates.

Photodesorption mechanism of water on WO3(001) - a combined embedded cluster, computational intelligence and wave packet approach.

In this work we investigate the mechanism of photodesorption of water from a WO3(001) surface by theoretical calculations, applying an embedded cluster model. Using the CASSCF method, we have calculated both the ground state as well as the energetically preferred charge-transfer state in three degrees of freedom of the water molecule on the surface. The calculated potential energy surfaces were afterwards fitted with a neural network optimized by a genetic algorithm. A final quantum dynamic wave packet study provided insight into the photodesorption mechanism.

Theoretical Studies on the Hydroaminoalkylation of Alkenes with Primary and Secondary Amines.

The α-alkylation of amines with alkenes catalyzed by early transition-metal complexes represents an efficient and atom economic method for the synthesis of functionalized amines from simple and easily available starting materials. While the successful use of secondary amines, such as dimethylamine, strongly underlines the enormous industrial potential of this reaction, the analogous intermolecular α-alkylation of primary amines, especially methylamine, remains an unsolved synthetic task to this day. Based on calculated thermodynamic data, these experimental findings can now be explained for the first time, whereby several competing reactions, which are explained in detail, are of crucial importance for the different behavior of primary and secondary amines.