Lecture on Protein Design and Its Potential

Introduction to Proteins

• Proteins are essential for biological functions:
  • Digest food
  • Contract muscles
  • Fire neurons
  • Power the immune system
• Proteins are chains of amino acids, folding into unique 3D structures.
• Folding is precise, occurring in fractions of a second.

Protein Structure and Function

• Shape determines function (e.g., hemoglobin and oxygen transport).
• Amino acid sequence determines protein shape and function.
• Genes in the genome specify these amino acid sequences.

The Protein Folding Problem

• Complex problem due to myriad possible shapes.
• Historically, humans have modified existing proteins slightly.
• Aimed to uncover fundamental principles of protein folding.

Advances in Computational Protein Design

• Breakthrough with the Rosetta computer program:
  • Design new proteins from scratch.
  • Encode amino acid sequences in synthetic genes.
• Decreasing gene synthesis costs and increased computing power enable large-scale design.
• New proteins can be synthesized in bacteria and tested for function and safety.

Exploring Protein Diversity

• Nature's proteins are a small sample of potential diversity.
• Nature uses 20 amino acids, typical protein chains are 100 amino acids long.
• Computational design allows exploration of vast protein possibilities.

Challenges and Applications

• Natural evolution solves existing biological challenges.
• Human challenges (diseases, ecological issues) require new proteins.
• Computational design can address these current challenges.

Applications of Protein Design

• Vaccines:
  • Design proteins that stimulate stronger immune responses.
  • Example: Respiratory virus RSV vaccine candidates.
• Therapeutics:
  • Break down gluten for celiac disease.
  • Stimulate immunity against cancer.

Vision for the Future

• Inspired by the digital revolution and Bell Laboratories.
• Aims to build a collaborative environment for protein design.
• Attracting global talent to accelerate the revolution.

Focus Areas

1. Universal Flu Vaccine:
   • One shot for lifetime flu protection.
2. Expanded Amino Acid Alphabet:
   • Design therapeutics using thousands of amino acids.
3. Targeted Delivery Vehicles:
   • Precise targeting of medications.
4. Smart Therapeutics:
   • Advanced therapeutics for specific immune cells.
5. Protein-based Materials:
   • Inspired by biological materials to solve energy and ecological challenges.

Participation and Outreach

• Institute is growing, seeking diverse scientists.
• Public participation through the Foldit game and Rosetta at Home project.

Conclusion

• Protein design aims to improve the world.
• Encouragement to join the protein design revolution.