Discovery of a new class of cell-penetrating peptides by novel phage display platform.

The primary hurdles for small interference RNA (siRNA) in clinical use are targeted and cytosolic delivery. To overcome both challenges, we have established a novel platform based on phage display, called NNJA. In this approach, a lysosomal cathepsin substrate is engineered within the flexible loops of PIII, that is displaying a unique random sequence at its N-terminus.

Structure-free antibody paratope similarity prediction for epitope binning via protein language models.

Antibodies are an important group of biological molecules that are used as therapeutics and diagnostic tools. Although millions of antibody sequences are available, identifying their structural and functional similarity and their antigen binding sites remains a challenge at large scale. Here, we present a fast, sequence-based computational method for antibody paratope prediction based on protein language models.

Instantaneous generation of protein hydration properties from static structures.

Complex molecular simulation methods are typically required to calculate the thermodynamic properties of biochemical systems. One example thereof is the thermodynamic profiling of (de)solvation of proteins, which is an essential driving force for protein-ligand and protein-protein binding. The thermodynamic state of water molecules depends on its enthalpic and entropic components; the latter is governed by dynamic properties of the molecule.

Optimization of a 1,3,4-oxadiazole series for inhibition of Ca/calmodulin-stimulated activity of adenylyl cyclases 1 and 8 for the treatment of chronic pain.

Adenylyl cyclases type 1 (AC1) and 8 (AC8) are group 1 transmembrane adenylyl cyclases (AC) that are stimulated by Ca/calmodulin. Studies have shown that mice depleted of AC1 have attenuated inflammatory pain response, while AC1/AC8 double-knockout mice display both attenuated pain response and opioid dependence. Thus, AC1 has emerged as a promising new target for treating chronic pain and opioid abuse.