Molecular Dynamics Study of Protein Aggregation at Moving Interfaces.

Repeated compression and dilation of a protein film adsorbed to an interface lead to aggregation and entry of film fragments into the bulk. This is a major mechanism for protein aggregate formation in drug products upon mechanical stress, such as shaking or pumping. To gain a better understanding of these events, we developed a molecular dynamics (MD) setup, which would, in a later stage, allow for in silico formulation optimization.

Thermodynamic Modeling and Experimental Data Reveal That Sugars Stabilize Proteins According to an Excluded Volume Mechanism.

We present a new thermodynamic model to investigate the relative effects of excluded volume and soft interaction contributions in determining whether a cosolute will either destabilize or stabilize a protein in solution. This model is unique in considering an atomistically detailed model of the protein and accounting for the preferential accumulation/exclusion of the osmolyte molecules from the protein surface. Importantly, we use molecular dynamics simulations and experiments to validate the model.

Catching a Moving Target: Comparative Modeling of Flaviviral NS2B-NS3 Reveals Small Molecule Zika Protease Inhibitors.

The pivotal role of viral proteases in virus replication has already been successfully exploited in several antiviral drug design campaigns. However, no efficient antivirals are currently available against flaviviral infections. In this study, we present lead-like small molecule inhibitors of the Zika Virus (ZIKV) NS2B-NS3 protease.