Lecture Notes on Protein Folding and Dynamics

General Information

• Presenter: Rohit Papu
• Topic: Protein folding and dynamics, focusing on charge-rich intrinsically disordered proteins (IDPs)
• Date: Not specified
• Format: Webinar
• Platform: YouTube

Introduction

• Rohit Papu is notable for his work on molecular driving forces behind protein interactions.
• Educational background includes physics, mathematics, electronics, and a Ph.D. in biological physics.
• Developed a strong research program at Washington University.

Key Research Areas

• IDPs and Phase Separation: Focus on cellular organization and neurodegeneration.
• Methods Development: Emphasis on simulations and designing new biomaterials.
• Recognition: Fellow of several scientific societies.

Main Discussion Points

Intrinsically Disordered Proteins (IDPs)

• Diagram of States: Explores conformations based on charge interactions.
• Polyamphalites: Major focus due to their presence in IDPs.
  • Types include polysviterions, blocky architectures, and random copolymers.

Biological Significance

• Nuclear Speckles and Membrane-less Organelles
  • RD repeats in nuclear speckles.
  • Speckle enrichment tied to arginine vs. lysine content.
  • Importance of mixing vs. segregation of charged residues.

Electrostatic and Solvation Effects

• Arginine vs Lysine
  • Differences in free energies of hydration.
  • Effects on structural stability and interactions.
• Hydration Asymmetry
  • Differences between bases and acids (e.g., Lysine vs Aspartate/Glutamate).

Phase Behavior and Conformations

• Bistability in Polysviterions
  • Observations of bistability between globules and self-avoiding walks.
  • Influence of sequence composition on stability and transitions.

Theoretical Models and Predictions

• Higgs and Joani Theory: Provides insights into compact globules and self-avoiding walks.
• Necklace Globules: Potentially metastable states influenced by sequence composition.

Methodological Insights

• Use of Thermodynamic Cycles
  • Addressing hydration complexities and ionization energies.
• Simulations
  • Absence simulations provide insights into phase behavior.

Practical Implications and Questions

• Charge Regulation
  • Potential for context-dependent PKA shifts and post-translational modifications.

Future Directions

• Experimental Validation: Further scrutiny by experimentalists is needed.
• Complex Ionic Mixtures: Understanding cellular milieu effects on IDPs.
• Dynamics of Conformational Interconversion: Potential for experimental observation.

Conclusion

• Emphasized importance of sequence composition and environmental conditions on IDP behavior.
• Encouraged continued research and experimentation to validate theoretical predictions.
• Thanked fellow researchers and collaborators for their contributions.