Modeling and Manipulating Biomolecular Interactions

This half of the course is taught by Prof. Ernest Fraenkel. This section contains lecture notes, reading material, and suggested study problems. There is also an associated protein design project.

Overview

Diverse problems ranging from fundamental questions of molecular biology to drug development can be analyzed in terms of the interactions between specific biomolecules, including protein-DNA and kinase-substrate interactions. Techniques for modifying these interactions are an essential part of the biological engineer's toolkit. This section of 20.320 will focus on methods for modeling and manipulating biomolecular interactions. By the end of this unit, you will know how to analyze biological networks and to re-engineer protein-protein and protein-drug complexes to make more potent biological agents.

Lecture Notes

These are Prof. Ernest Fraenkel's lecture notes.

TOPICS
Introduction: Modeling and Manipulating Biomolecular Interactions (PDF)
Protein Structure and Energetics (PDF)
Interaction Specificity (PDF - 1.6MB)
Molecular Design Part 1 (PDF - 1.1MB)
Modeling Disease (PDF)
Protein Structure Prediction (PDF)
Network Modeling (PDF)

Teaching assistants Daniel Martin-Alarcon and Allison Claas took these lecture notes during class.

LEC # TOPICS
12 This resource may not render correctly in a screen reader.Predictive models of biology, genome editing, sensors, light-activated proteins, new enzymes, electrostatics (PDF - 1.4MB)
13 This resource may not render correctly in a screen reader.Hydrogen bonding, the hydrophobic effect, how we represent proteins (PDF - 2.4MB)
14 Paralogues and orthologues, protein therapeutics (PDF) (These lecture notes are incomplete.)
15 This resource may not render correctly in a screen reader.Specificity (PDF)
16 The metropolis algorithm (PDF)
17 This resource may not render correctly in a screen reader.Gradient descent, molecular dynamics, ΔΔG for small molecules, pharma priorities (PDF - 1.8MB)
18 This resource may not render correctly in a screen reader.Drug development case study: Imatinib (PDF)
20

Guest lecture by Rebecca L. Carrier: This resource may not render correctly in a screen reader.Impact of drug delivery of effectiveness (PDF)

Courtesy of Rebecca L. Carrier. Used with permission.
21 This resource may not render correctly in a screen reader.Protein folding: thermodynamics (PDF - 1.9MB)
22 This resource may not render correctly in a screen reader.Kinetics of folding, predicting protein structure (PDF - 2.2MB)
23 This resource may not render correctly in a screen reader.Structure from sequence (PDF - 1.3MB)
24 This resource may not render correctly in a screen reader.Kinases, graph theory, experimental and computational techniques (PDF - 1.3MB)

Reading Material (Optional)

Scheeff, Eric D., and J. Lynn Fink. "Fundamentals of Protein Structure." In Structural Bioinformatics. Edited by Philip E. Bourne, and Helge Weissig. Wiley-Liss, 2003, pp. 15–39. ISBN: 9780471201991. [Preview with Google Books]

Grinstead, Charles M., and J. Laurie Snell, eds. This resource may not render correctly in a screen reader.Introduction to Probability (PDF - 3.06MB). American Mathematical Society, 1997. ISBN: 9780821807491. [Preview with Google Books]

Woolf, Peter, Burge Christopher, et al. Statistics and Probability Primer for Computational Biologists (PDF). 2004. (Courtesy of the authors. Used with permission.)