The Rosetta software for macromolecular modeling, docking and design is extensively used
in laboratories worldwide. During two decades of development by a community of …

Approximately 75% of all disease-relevant human proteins, including those involved in
intracellular protein–protein interactions (PPIs), are undruggable with the current drug …

We use computational design coupled with experimental characterization to systematically
investigate the design principles for macrocycle membrane permeability and oral …

Molecular chameleons possess a flexibility that allows them to dynamically shield or expose
polar functionalities in response to the properties of the environment. Although the concept …

Small macrocycles with four or fewer amino acids are among the most potent natural
products known, but there is currently no way to systematically generate such compounds …

The computational de novo protein design is increasingly applied to address a number of
key challenges in biomedicine and biological engineering. Successes in expanding …

Conformational flexibility has been proposed to significantly affect drug properties outside
rule-of-5 (Ro5) chemical space. Here, we investigated the influence of dynamically exposed …

As a versatile therapeutic modality, peptides attract much attention because of their great
binding affinity, low toxicity, and the capability of targeting traditionally “undruggable” protein …

Recent progress in de novo protein design has led to an explosion of new protein structures,
functions and assemblies. In this essay, I consider how the successes and failures in this …

Cyclic peptides are among the most diverse architectures for current drug discovery efforts.
Their size, stability, and ease of synthesis provide attractive scaffolds to engage and …