Beyond native sequence recovery: Improved modeling of the sequence-energy landscape of protein structures
1. A new study by Foster Birnbaum and Amy E. Keating challenges the conventional approach of optimizing protein sequence design models solely for native sequence recovery (NSR). They demonstrate that focusing on NSR may not always align with more critical metrics like sequence-structure compatibility and mutation energy prediction.
2. The authors introduce PottsMPNN, a novel model that learns a Potts energy function from protein backbones. This approach reduces NSR but significantly improves sequence generation and energy prediction capabilities, highlighting the limitations of using NSR as the primary optimization metric.
3. Training with noisy backbone structures and multiple sequence alignments (MSAs) further enhances model performance. These strategies prevent overfitting to NSR and improve the model's ability to generate sequences that fold into desired structures and predict mutation effects accurately.
4. The study emphasizes the importance of capturing pairwise interactions in protein sequences through the Potts model. This method allows PottsMPNN to outperform existing models in predicting the energetic effects of mutations and optimizing sequence-structure compatibility.
5. The results suggest that future protein design models should focus on more biologically relevant objectives rather than solely maximizing NSR. This shift in focus could lead to more effective and versatile protein design tools with broader applications in biotechnology and medicine.
📜Paper: https://t.co/NSyHNpQzg1
💻Code: https://t.co/4xU8woAOLH
#ProteinDesign #MachineLearning #ComputationalBiology #PottsModel #ProteinEngineering
Congrats to @MontclareLabs @dustygr8britton Hao-Wei Shih, Chengliang Liu, Sihan Jia & collabs Min-Woo Kim, Mia Klopfenstein from @LeeLab_nyu, Suman Maity from @Atanu_Acharya1 Lab on getting our photoconductive proteins out! https://t.co/dQ2CLMcIp8 https://t.co/dQ2CLMcIp8
I, and every scientist I've talked to, believe the end result of this devastating cut will be that Universities will simply pass on the buck to investigators. Many of us fervently agree that university administrations & bureaucracy should be downsized and reformed. This maneuver is going to do nothing to actually instigate that change, it is simply going to result in a giant DIRECT cut to biomedical science in this country that is going to cripple science, lead to layoffs of hardworking students and postdocs with big dreams who are the country's future, and destroy this country's scientific pre-eminence. I personally find it hard to fathom how Elon Musk and pals, who clearly understand the value and beauty of science deeply, could not see this endgame and...hesitate. This is matricide. @shaunmmaguire@elonmusk
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Cutting-edge cancer treatments research promises more effective https://t.co/IfYcwXuRnx
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#welldone
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