Youwen Zhuang

Fine-tuning an intracellular allosteric pocket programs GPCR signaling bias

This study fine-tunes an intracellular allosteric pocket of NTSR1 to program GPCR signaling bias, revealing how ligand modifications alter transducer coupling and downstream signaling.

Multi-vector retrieval enables residue-resolved prediction of protein partners by ColBERT-PPI

ColBERT-PPI predicts protein partners and their binding sites at the residue level using a multi-vector framework, outperforming existing methods on benchmark datasets.

Molecular principles for graded activation of dopamine D1 receptor

The paper defines the molecular mechanism of graded activation of the dopamine D1 receptor and shows how ligand efficacy is encoded through an activation pathway.

Accurate de novo design of peptides from programming biophysical landscape

NeoPep designs functional peptides de novo using a deep-learning framework that models biophysical principles, achieving high hit rates and structural accuracy across diverse targets.

Multiple Allosteric Sites Allow for Synergistic Enhancement of GPCR Signaling

The paper identifies multiple allosteric sites on the D1 dopamine receptor that allow synergistic enhancement of GPCR signaling through combined positive allosteric modulators.

Mechanism of dopamine binding and allosteric modulation of the human D1 dopamine receptor

The paper reports the structures of D1R-Gs complex bound to dopamine and LY3154207, revealing mechanisms of dopamine recognition and allosteric modulation for drug discovery.