Day 1 – Tuesday, 14th May 2024
| Time | Event |
| 9:00 a.m. | Check in + Breakfast |
| 9:30 a.m. | Welcome and introduction to protein structure (by organizers) |
| 10:00 a.m. | Plenary Lecture by Prof. Andrew McShan: “The coming of age of de novo protein design” |
| 11:15 a.m. | PyMOL Tutorial |
| 12:00 p.m. | Lunch |
| 12:45 p.m. | PyMOL Tutorial (cont.) |
| 1:15 p.m. | Introduction to AlphaFold 2 (Sections 1-3) |
| 2:15 p.m. | Coffee Break |
| 2:35 p.m. | Analysis of predictions and challenge problem (Sections 4-5) |
| 3:30 p.m. | Wrapping up Day 1 |
Day 2 – Wednesday, 15th May 2024
| Time | Event |
| 9:30 a.m. | Social + Breakfast |
| 10:00 a.m. | Plenary lecture by Prof. Jeff Skolnick: “Predicting protein interactions of the kinase Lck critical to T cell modulation” |
| 11:15 a.m. | Predicting the effects of mutations (Section 6) |
| 12:00 p.m. | Lunch |
| 12:45 p.m. | AF2 Multimer / AF3 comparison (Section 7) |
| 1:15 p.m. | RFdiffusion Tutorial (Section 8) |
| 2:15 p.m. | Coffee break |
| 2:30 p.m. | Protein design competition |
| 3:00 p.m. | Prize distribution and wrap up |
“The coming of age of de novo protein design“
De novo protein design involves the interplay between a desired structure backbone and generation of corresponding amino acid sequences, typically distinct from proteins observed in nature. Conventional approaches for protein design exploit our knowledge of first principles of protein folding using biophysical energy functions. Recently, the application of bioinformatics and novel machine learning algorithms has catalyzed a renaissance in de novo protein design enabling novel protein folds, enzymes, biosensors, biomaterials, inhibitors, and fold-switching proteins. Here, state of the art methods for de novo protein design will be outlined. Computational design and experimental validation of several designed proteins with therapeutic potential will be presented.
“Predicting protein interactions of the kinase Lck critical to T cell modulation”
Very recently, deep learning-based approaches have made significant progress in predicting the structures of protein complexes. We describe the application of AF2 Complex to search for interactors of the regulatory domains (SH2 and SH3) of the protein kinase Lck, which is essential for T cell activation among about 1000 human proteins involved in adaptive immune responses. We describe how Lck may be specifically targeted by a palmitoyltransferase using a phosphotyrosine motif. We uncover “hot-spot” interactions between Lck and the tyrosine phosphatase CD45, leading to a significant conformational shift of Lck for activation. Lastly, we present intriguing interactions between the phosphotyrosine-binding domain of Lck and the cytoplasmic tail of the immune checkpoint LAG3 and propose a molecular mechanism for its inhibitory role. Together, this multifaceted study provides valuable insights into the complex landscape of T cell regulation and signaling.