Mission & Research Objectives
Our mission is to improve protein structure prediction and design models, specifically focusing on cancer-related mutant proteins.
Core Objectives:
- Structure Prediction: Predict structures of cancer-driver or drug-resistant mutant proteins.
- Antibody Design: Design corresponding de novo antibodies based on predicted structures.
Research Plan & Milestones
Our three-year research strategy is divided into progressive phases aimed at clinical integration and model optimization.
Phase 1: Initial Modeling & Validation
Focus on critical mutant proteins including KRAS G12X and EGFR C797S. Use cryo-EM data to refine the AlphaFold backbone and validate biological function in vitro and in vivo.
Phase 2: De Novo Antibody Development
Utilize the Rosetta model to predict antibodies targeting validated mutant structures. Conduct binding affinity tests and integrate this feedback to optimize the design model.
Phase 3: Model Tuning & Scaling
Apply learned optimization "tips" to extend predictions to other important mutant proteins. Establish a robust pipeline that requires fewer physical experiments for new targets.
Core Innovation
"Our core idea is to integrate information from current established AI models with real cryo-EM and biological experiments to develop AI models with high accuracy and to provide solutions to clinical unmet needs."
By treating experimental data as a new component in the learning model—similar to the impact of Multiple Sequence Alignment (MSA) in previous breakthroughs—we aim to transform how AI models are tuned for precision medicine.
Research Team
| Role |
Name |
Affiliation |
| Research Group PI | 陳璿宇 (Hsuan-Yu Chen) | Institute of Statistical Science (ISS) |
| Co-PI | 杜憶萍 (I-Ping Tu) | Institute of Statistical Science (ISS) |
| Co-PI | 袁新盛 (Shin-Sheng Yuan) | Institute of Statistical Science (ISS) |
| Co-PI | 章為皓 (Wei-Hau Chang) | Institute of Biological Chemistry (IoC) |
| Co-PI | 陳玉如 (Yu-Ju Chen) | Institute of Biological Chemistry (IoC) |
| Co-PI | 張雅媗 (Ya-Hsuan Chang) | National Health Research Institutes (NHRI) |
| Co-PI | 黃國彥 (Kuo-Yen Huang) | National Taiwan University (NTU) |
References
- LoPiccolo J, Gusev A, Christiani DC, Jänne PA. Lung cancer in patients who have never smoked — an emerging disease. Nature Reviews Clinical Oncology 2024;21(2):121-146.
- Abramson J, Adler J, Dunger J, et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 2024;630(8016):493-500.
- Varadi M, Bertoni D, Magana P, et al. AlphaFold Protein Structure Database in 2024: providing structure coverage for over 214 million protein sequences. Nucleic Acids Res 2024;52(D1):D368-D375.
- Simons KT, Bonneau R, Ruczinski I, Baker D. Ab initio protein structure prediction of CASP III targets using ROSETTA. Proteins 1999;Suppl 3:171-6.
- Huang P-S, Boyken SE, Baker D. The coming of age of de novo protein design. Nature 2016;537(7620):320-327.
- Jiang L, Althoff EA, Clemente FR, et al. De Novo Computational Design of Retro-Aldol Enzymes. Science 2008;319(5868):1387-1391.