Smooth particle mesh Ewald-integrated stochastic Lanczos many-body dispersion algorithm.

We derive and implement an alternative formulation of the Stochastic Lanczos algorithm to be employed in connection with the Many-Body Dispersion model (MBD). Indeed, this formulation, which is only possible due to the Stochastic Lanczos' reliance on matrix-vector products, introduces generalized dipoles and fields. These key quantities allow for a state-of-the-art treatment of periodic boundary conditions via the O(Nlog(N)) Smooth Particle Mesh Ewald (SPME) approach which uses efficient fast Fourier transforms.

Generalized Many-Body Dispersion Correction through Random-Phase Approximation for Chemically Accurate Density Functional Theory.

We extend our recently proposed Deep Learning-aided many-body dispersion (DNN-MBD) model to quadrupole polarizability () terms using a generalized Random Phase Approximation (RPA) formalism, thus enabling the inclusion of van der Waals contributions beyond dipole. The resulting DNN-MBDQ model only relies on -derived quantities as the introduced quadrupole polarizabilities are recursively retrieved from dipole ones, in turn modeled via the Tkatchenko-Scheffler method. A transferable and efficient deep-neuronal network (DNN) provides atom-in-molecule volumes, while a single range-separation parameter is used to couple the model to Density Functional Theory (DFT).

Accurate Deep Learning-Aided Density-Free Strategy for Many-Body Dispersion-Corrected Density Functional Theory.

Using a deep neuronal network (DNN) model trained on the large ANI-1 data set of small organic molecules, we propose a transferable density-free many-body dispersion (DNN-MBD) model. The DNN strategy bypasses the explicit Hirshfeld partitioning of the Kohn-Sham electron density required by MBD models to obtain the atom-in-molecules volumes used by the Tkatchenko-Scheffler polarizability rescaling. The resulting DNN-MBD model is trained with minimal basis iterative Stockholder atomic volumes and, coupled to density functional theory (DFT), exhibits comparable (if not greater) accuracy to other approaches based on different partitioning schemes.

Variational formulation of the bond capacity charge polarization model.

We present an alternative energy formulation of the bond capacity charge polarization model to be used in molecular dynamics simulations. The energy expression consists of a Coulombic charge-charge interaction contribution as well as a quadratic Coulomb potential term, which can be seen as the electrostatic energy stored in the system's bond capacities. This formulation is shown to be variational in the potential space, although, it shares the same set of charges with the original non-variational formulation of the model.

Stochastic Evaluation of Many-Body van der Waals Energies in Large Complex Systems.

We propose a new strategy to solve the key equations of the many-body dispersion (MBD) model by Tkatchenko, DiStasio Jr., and Ambrosetti. Our approach overcomes the original computational complexity that limits its applicability to large molecular systems within the context of density functional theory.

Polarizable charges in a generalized Born reaction potential.

The generalized Born (GB) model is a fast implicit solvent model that is used as an approximation to the Poisson equation for solutes described by point charges. Due to the simple analytical form, GB models are widely used in molecular dynamics simulations to account for (implicit) solvation effects. In this work, we extend the application of the GB model to polarizable charges by coupling it to the bond capacity (BC) model.

Molecular, Macromolecular, and Supramolecular Glucuronide Prodrugs: Lead Identified for Anticancer Prodrug Monotherapy.

In this work, a tumor growth intervention by localized drug synthesis within the tumor volume, using the enzymatic repertoire of the tumor itself, is presented. Towards the overall success, molecular, macromolecular, and supramolecular glucuronide prodrugs were designed for a highly potent toxin, monomethyl auristatin E (MMAE). The lead candidate exhibited a fold difference in toxicity between the prodrug and the drug of 175, had an engineered mechanism to enhance the deliverable payload to tumours, and contained a highly potent toxin such that bioconversion of only a few prodrug molecules created a concentration of MMAE sufficient enough for efficient suppression of tumor growth.

Molecular Dynamics Using Nonvariational Polarizable Force Fields: Theory, Periodic Boundary Conditions Implementation, and Application to the Bond Capacity Model.

We extend the framework for polarizable force fields to include the case where the electrostatic multipoles are not determined by a variational minimization of the electrostatic energy. Such models formally require that the polarization response is calculated for all possible geometrical perturbations in order to obtain the energy gradient required for performing molecular dynamics simulations. By making use of a Lagrange formalism, however, this computationally demanding task can be replaced by solving a single equation similar to that for determining the electrostatic variables themselves.

Including implicit solvation in the bond capacity polarization model.

We derive expressions corresponding to a coupling of the recently proposed Bond Capacity polarization model with implicit solvation by means of the generalized Born and conductor-like polarizable continuum models. The original bond capacity interaction kernel is in both cases augmented with a term that accounts for the reaction potential arising from the continuum. The expressions for energy gradients are derived within the recently introduced Lagrangian formalism for the efficient evaluation of energy gradients of nonvariational force fields.

Describing Molecular Polarizability by a Bond Capacity Model.

We propose a bond capacity model for describing molecular polarization in force field energy functions at the charge-only level. Atomic charges are calculated by allowing charge to flow between atom pairs according to a bond capacity and a difference in electrostatic potential. The bond capacity is closely related to the bond order and decays to zero as the bond distance is increased.