An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity.

Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase that plays an oncogenic role in breast, gastric and other solid tumors. However, anti-HER2 therapies are only currently approved for the treatment of breast and gastric/gastric esophageal junction cancers and treatment resistance remains a problem. Here, we engineer an anti-HER2 IgG1 bispecific, biparatopic antibody (Ab), zanidatamab, with unique and enhanced functionalities compared to both trastuzumab and the combination of trastuzumab plus pertuzumab (tras + pert).

Method for Slater-Type Density Fitting for Intermolecular Electrostatic Interactions with Charge Overlap. I. The Model.

The effects of charge overlap, or charge penetration, are neglected in most force fields and interaction terms in QM/MM methods. The effects are however significant at intermolecular distances near the van der Waals minimum. In the present study, we propose a method to evaluate the intermolecular Coloumb interaction using Slater-type functions, thus explicitly modeling the charge overlap.

Accuracy of typical approximations in classical models of intermolecular polarization.

One of the largest limitations of standard molecular-mechanics force fields is the neglect of intermolecular polarization. Several attempts to cure this problem have been made, but the results have not always been fully satisfactory. In this paper, we present a quantitative study of the fundamental approximations that underlie polarization models for classical force fields.

Many-Body Polarization, a Cause of Asymmetric Solvation of Ions and Quadrupoles.

Three models are used to study the effect of many-body polarization in the solvation of non-dipolar molecules and ions in water. Two of the models are very simplified and are used to show a number of basic principles of correlation of solvent degrees of freedom and asymmetric solvent structures. These principles are used to interpret results from the third model:  an accurate simulation of para-benzoquinone (PBQ) in aqueous solution with a combined quantum chemical statistical mechanical solvent model with an explicit solvent.

Simulations of the absorption and fluorescence of indole in aqueous solution and at a nonpolar/polar interface.

Theoretical results are presented on the absorption and fluorescence of indole in aqueous solution as well as at the air/water surface. We use a combined quantum chemical statistical mechanical model with explicit solvent. An approximate ab initio complete active space self-consistent field description of the indole molecule is used, coupled to a discrete polarizable water medium.

Planar or nonplanar: what is the structure of urea in aqueous solution?

A combined quantum chemical statistical mechanical method has been used to study the solvation of urea in water, with emphasis on the structure of urea. The model system consists of three parts: a Hartree-Fock quantum chemical core, 99 water molecules described with a polarizable force-field, and a dielectric continuum. A free-energy profile along the transition of urea from planar to a nonplanar structure is calculated.

p-Benzoquinone in aqueous solution: Stark shifts in spectra, asymmetry in solvent structure.

Results from a simulation of p-benzoquinone (PBQ) in water is presented. An explicit solvent representation is used together with a multiconfigurational ab initio quantum chemical method. The electronic n --> pi* transitions are studied in aqueous solution and the two such transitions are both blue-shifted but to different degree.

pi --> n fluorescence transition in formaldehyde in aqueous solution: a combined quantum chemical statistical mechanical study.

The solvent shift to the fluorescence transition pi --> n in formaldehyde in aqueous solution is theoretically analyzed. The solvent model has explicit representation of the solvent and uses the complete active space state interaction (CASSI) method to obtain a description of the wave function of the solute similar to what the complete active space self-consistent-field (CASSCF) method would give. In the description of the solute-solvent interaction the discrete set of solvent molecules perturb the solute not only through an electrostatic perturbation but also through a nonelectrostatic operator.