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 on Canvas. 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 | Course Overview. Introductions. High Performance Computing. Basic Linux. [pptx/pdf]. Exercise 0: Basic Linux + Treasure Hunt. [Markdown]. |
| W | 01/14 | Jupyter Notebooks. Software Environments. [pptx/pdf]. Exercise 1: Introduction to Jupyter Notebooks. [Notebook]. |
| M | 01/19 | No class - MLK Day |
| W | 01/21 | Fundamentals of biological macromolecules. [pptx/pdf]. Exercise 2: Structural visualization and alignment. [Notebook]. Due: Exercise 0. |
| F | 01/23 | Structure determination by X-ray crystallography, NMR, and CryoEM. [pptx/pdf]. Due: Exercise 1. |
| M | 01/26 | Structure prediction. Homology modeling. Deep neural network methods. [pptx/pdf]. Exercise 3: Protein complex prediction using ColabFold. [Notebook]. |
| W | 01/28 | Selecting a target for structure-based molecular design. Scientific and market considerations. [pptx/pdf]. Due: Exercise 2. |
| M | 02/02 | G protein-coupled receptors. Molecular pharmacology. Concentration Response Curves. Efficacy and Biased Agonism. Mechanisms of (biased) signaling. Computational studies. [pptx/pdf]. Due: Exercise 3. Quiz: Biomolecular structure. |
| W | 02/04 | Scientific literature and databases. Biochemistry-related databases. Academic literature search and reference management with Zotero (Guest: Sean Murphy, library). [pptx/pdf]. |
| M | 02/09 | Electrostatics and solvation of biological macromolecules. [pptx/pdf]. |
| W | 02/11 | Exercise 4: Visualizing protonation and electrostatics. [Notebook]. |
| M | 02/16 | Molecular docking. Scoring functions. Common optimization algorithms. [pptx/pdf]. |
| W | 02/18 | Exercise 5: Molecular docking with AutoDock Vina. [Notebook]. 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. [Notebook]. Due: Biological target report draft (optional).. |
| W | 03/04 | Molecular mechanics force fields. Bonded and nonbonded energy terms. Parameterization. [pptx/pdf]. |
| M | 03/09 | Monte Carlo. Monte Carlo Integration. Markov chain Monte Carlo [pptx/pdf]. Due: Biological target report.. |
| W | 03/11 | Exercise 7: Preparing a system for molecular simulation. [Notebook]. Due: Exercise 6.. |
| M | 03/16 | No class - Spring Break |
| W | 03/18 | No class - Spring Break |
| M | 03/23 | Catch up on exercises / work on projects. Due: Quiz: Potential energy.. |
| W | 03/25 | Molecular simulation. Metropolis Monte Carlo. Molecular dynamics. Constrained dynamics. Integrators, thermostats, and barostats. Equilibration. Visualization of trajectories. [pptx/pdf]. Exercise 8: Performing a molecular simulation. [Notebook]. Due: Exercise 7. |
| M | 03/30 | Enhanced sampling. Importance sampling. Thermodynamic processes. Umbrella sampling. Multi-state Analysis. [pptx/pdf]. Exercise 9: Umbrella sampling. [Notebook]. |
| W | 04/01 | Replica Exchange [pptx/pdf]. Exercise 10: Performing replica exchange with Fulton Market. [Notebook]. Due: Exercise 8. |
| M | 04/06 | Exploratory data analysis of molecular simulations. Fluctuation analysis. Dimensionality reduction. Clustering. Contact analysis. Exercise 11: Analyzing molecular dynamics simulations. [Notebook]. Due: Exercise 9. |
| W | 04/08 | Free energy calculations. Thermodynamic cycles. Alchemical methods. End-point methods. Implicit ligand theory. [pptx/pdf]. |
| M | 04/13 | Exercise 12: End-point binding free energy calculations. [Notebook]. |
| W | 04/15 | Quantitative structure-property relationships. Structural features. Common properties. Machine learning methods. [pptx/pdf]. |
| M | 04/20 | Solubility. [pptx/pdf]. Exercise 13: Machine learning prediction of solubility. [Notebook]. |
| W | 04/22 | Quantum mechanics/molecular mechanics (QM/MM) [pptx/pdf]. Due: Exercise 10 and 11. Quiz: Molecular simulations. |
| M | 04/27 | Exercise 14: QM/MM analysis of SARS-CoV-2 MPro catalysis. [Notebook]. Due: Exercise 12. |
| W | 04/29 | Catch up on exercises / work on projects. Due: Exercise 13. 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.