Lecture slides and exercise notebooks should be available below after the class period. If they are not, please let me know.
| M | 8/22 | Introduction and syllabus [key/ppt/pdf]. Exercise 1: Introduction to Google Colab [colab]. |
| W | 8/24 | Fundamentals of biological macromolecules [key/ppt/pdf]. Exercise 2: Structural visualization and alignment [colab]. |
| M | 8/29 | Structure determination by X-ray crystallography, NMR, and CryoEM [key/ppt/pdf]. Due: Exercise 1. |
| W | 8/31 | Structure prediction [key/ppt/pdf]. Exercise 3: Modeling Cytochrome P450 structure with ColabFold [colab]. Due: Exercise 2. |
| M | 9/5 | No class - Labor Day |
| W | 9/7 | Selecting a target for structure-based molecular design. Scientific and market considerations [key/ppt/pdf]. |
| M | 9/12 | Surveying the scientific literature. Academic literature databases. Reference management with Zotero [key/ppt/pdf]. Due: Exercise 3. Quiz: Biomolecular structure. |
| W | 9/14 | Pharmaceutical ethics. Access to medicines versus incentivizing research and development. Informed consent in clinical trials [key/ppt/pdf]. |
| M | 9/19 | Electrostatics and solvation of biological macromolecules [key/ppt/pdf]. |
| W | 9/21 | Exercise 4: Visualizing protonation and electrostatics [colab]. Due: Ethics discussion report. |
| M | 9/26 | Biological target presentations. Due: Biological target presentation. |
| W | 9/28 | Biological target presentations. Due: Exercise 4. |
| M | 10/3 | No class - professor at conference |
| W | 10/5 | Molecular docking. Scoring functions. Common optimization algorithms [key/ppt/pdf]. Exercise 5: Molecular docking with AutoDock Vina, during lunch [colab]. Due: Biological target report. |
| M | 10/10 | No class - Fall break day |
| W | 10/12 | Molecular mechanics force fields. Bonded and nonbonded energy terms. Parameterization [key/ppt/pdf]. Due: Exercise 5. |
| M | 10/17 | Exercise 6: Preparing a system for molecular simulation [colab]. |
| W | 10/19 | Quantum mechanics/molecular mechanics (QM/MM) [key/ppt/pdf]. |
| M | 10/24 | Exercise 7: QM/MM analysis of MPro catalysis [colab]. Due: Exercise 6. |
| W | 10/26 | Monte Carlo. Monte Carlo Integration. Markov chain Monte Carlo [key/ppt/pdf]. Quiz: Potential energy. |
| M | 10/31 | Molecular simulation. Metropolis Monte Carlo. Molecular dynamics. Constrained dynamics. Integrators, thermostats, and barostats [key/ppt/pdf]. Exercise 8: Performing a molecular simulation with OpenMM [colab]. Due: Exercise 7. |
| W | 11/2 | Analysis of molecular simulation. Equilibration. Alignment and visualization of trajectories. Root mean square properties. Estimating expectation values. Dimensionality reduction. Exercise 9: Analysis of molecular dynamics [colab]. |
| M | 11/7 | Simulating and analyzing thermodynamic processes. Thermodynamic processes. Umbrella sampling. Replica exchange. Statistical estimation of expectations and free energies [key/ppt/pdf]. Due: Exercise 8. |
| W | 11/9 | Binding free energy calculations. Alchemical methods. Thermodynamic cycles. [key/ppt/pdf]. Exercise 10: Umbrella sampling [colab]. Due: Exercise 9. |
| M | 11/14 | Analysis of binding free energy calculations. Simulation quality metrics. Pose prediction. Exercise 11: YANK [colab]. |
| W | 11/16 | Quantitative structure-property relationships. Structural features. Common properties. Machine learning methods. [key/ppt/pdf]. Due: Exercise 10. Quiz: Molecular simulations. |
| M | 11/21 | Exercise 12: Machine learning [colab]. Due: Exercise 11. |
| W | 11/23 | No class - Thanksgiving break |
| M | 11/28 | Final presentations Due: Exercise 12. Final presentation. |
| W | 11/30 | Final presentations |
| F | 12/2 | Innovation Day |
| F | 12/9 | Due: Final reports. |