There will be 30 class sessions over 16 weeks. A tentative schedule is below.
Lecture slides and exercise notebooks should be available below after the class period. If they are not, please let me know.
There are optional deadlines to submit drafts. If you submit a draft by the optional deadline, I plan to provide feedback within two days about whether the draft is satisfactory and the steps that you could take to make it satisfactory.
| M | 01/12 | Introduction and syllabus. Basic Linux and remote computing. Logging in. Terminal. Linux commands. Paths. Environments. GitHub and Git. |
| W | 01/14 | Exercise 1: Introduction to Jupyter notebooks. |
| M | 01/19 | No class - MLK Day |
| W | 01/21 | Fundamentals of biological macromolecules. Exercise 2: Structural visualization with py3DMol. Due: Exercise 1. |
| F | 01/23 | Structure determination by X-ray crystallography, NMR, and CryoEM. |
| M | 01/26 | Structure prediction. Homology modeling. AlphaFold and RoseTTAFold Exercise 3: Homology modeling. |
| W | 01/28 | Selecting a target for structure-based molecular design. Scientific and market considerations Due: Exercise 2. |
| M | 02/02 | G protein-coupled receptors. Molecular pharmacology. Levels of efficacy. Binding and functional selectivity. |
| W | 02/04 | Scientific literature and databases. Academic literature databases. Reference management with Zotero. PubChem, PDB, UniProt, and GPCRdb. Due: Exercise 3. Quiz: Biomolecular structure. |
| M | 02/09 | Electrostatics and solvation of biological macromolecules. |
| W | 02/11 | Exercise 4: Visualizing protonation and electrostatics. |
| M | 02/16 | Molecular docking. Scoring functions. Common optimization algorithms. |
| W | 02/18 | Exercise 5: Molecular docking with AutoDock Vina. Due: Exercise 4. Biological target presentation draft (optional). |
| M | 02/23 | Biological target presentations. Due: Biological target presentations. |
| W | 02/25 | Biological target presentations. Decide project teams. Due: Exercise 5. |
| M | 03/02 | Virtual screening on high performance computing resources. Chemical library preparation. Job submission. Exercise 6: Virtual Screening. Due: Biological target report draft (optional).. |
| W | 03/04 | Molecular mechanics force fields. Bonded and nonbonded energy terms. Parameterization. |
| M | 03/09 | Exercise 7: Preparing a system for molecular simulation. Due: Exercise 6. Biological target report.. |
| W | 03/11 | Monte Carlo. Monte Carlo Integration. Markov chain Monte Carlo Due: Quiz: Potential energy. |
| M | 03/16 | No class - Spring Break |
| W | 03/18 | No class - Spring Break |
| M | 03/23 | Molecular simulation. Metropolis Monte Carlo. Molecular dynamics. Constrained dynamics. Integrators, thermostats, and barostats. Equilibration. Exercise 8: Performing a molecular simulation with OpenMM. Due: Exercise 7. |
| W | 03/25 | Simulation Analysis. Alignment and visualization of trajectories. Root mean square properties. Estimating expectation values. Dimensionality reduction. Clustering. Exercise 09: Analysis of molecular simulations. |
| M | 03/30 | Catch up on exercises / work on projects. Due: Exercise 8 (end of class). |
| W | 04/01 | Enhanced sampling. Importance sampling. Thermodynamic processes. Umbrella sampling. Multi-state Analysis. Exercise 10: Umbrella sampling. Due: Exercise 9. |
| M | 04/06 | Replica Exchange. Exercise 11: Performing replica exchange with Fulton Market. |
| W | 04/08 | Free energy calculations. Thermodynamic cycles. Alchemical methods. End-point methods. Implicit ligand theory. Due: Exercise 10. |
| M | 04/13 | Exercise 12: Free energy calculations with AlGDock. Due: Exercise 11. |
| W | 04/15 | Quantitative structure-property relationships. Structural features. Common properties. Machine learning methods. Due: Quiz: Molecular simulations. |
| M | 04/20 | Solubility. Exercise 13: Machine learning prediction of solubility. Due: Exercise 12. |
| W | 04/22 | Quantum mechanics/molecular mechanics (QM/MM) |
| M | 04/27 | Exercise 14: QM/MM analysis of SARS-CoV-2 MPro catalysis. Due: Exercise 13. |
| W | 04/29 | Catch up on exercises / work on projects. Due: Final presentation draft (optional). |
During the final exam period (TBD), students will give a final presentation. Exercise 14 is due on May 4 at noon. If you submit a draft of the final report by May 5, I will give you feedback by May 7. The final report and individual contribution report are due on May 11 at noon.