Course Title: BIOEN 488/588, Computational Protein Design

Instructor: Valerie Daggett

Credits: 4

UW general catalog course description: Explores methods in protein engineering, emphasizing biomedical and biotechnological applications. Includes molecular visualization, homology modeling, molecular dynamics, computational protein design, and evaluation of designs. Introduces current research in subject area. Students learn to use and apply computational tools to investigate design problems.

Prerequisites by Course: BIOEN 315 (for 488)

Prerequisites by Topic: Biochemical Molecular Engineering

Overview: Course covers current methods in protein engineering with an emphasis on biomedical and biotechnological applications. Topics include molecular visualization, homology modeling, molecular dynamics, and computational protein design. Students will learn how to use these tools through lectures and lab time and will apply them to investigate a problem of their choosing during the second half of the quarter. The course will also introduce students to current research in these areas.

 Textbook / resources:

n lucem molecular mechanics


Computational Biology Tools

Course Objectives:

By the end of the course, students should be able to:

  • Students will learn how to use tools of molecular modeling
  • Students will learn to make and evaluate molecular models of proteins
  • Students will learn how to computationally design and evaluate proteins for specified purposes

Topics Covered:

  1. Molecular visualization
  2. Homology modeling
  3. Molecular dynamics
  4. Computational protein design

Course Schedule: Classes meet Mondays 12:30 – 1:50 pm and Wednesdays at 1:30-2:50 pm
Labs meet Fridays 11:30-3:30pm (11:30-2:30 or 12:30-3:30)

Computer Use: Students will learn computational protein design using Rosetta, Chimera, BLAST and Modeller.  Software and computers are available in the Advanced Computing Laboratory, Foege N 140.

Laboratory Projects: Each lab is due at the beginning of lab the following week. Weeks 6-10 will be spent working on a project which will depend on which class the student is enrolled in. Week 10 will be presentations.

Lab 1 (Due 10/5): Intro to Sequence, Structure, and Homology Modeling with MODELLER UCSF Chimera,MODELLER

Lab 2 (Due 10/12):      Intuitive Design, Rosetta Design WT MD Analysis

Lab 3 (Due 10/19):      MD Simulations: WT full, RD full, WT fragment, designed fragment

Lab 4 (Due 10/26):      MD Analysis, Generation II Design and Simulation

Lab 5 (Due 11/2): Generation II Analysis, Final Write-up. Formal write-up in standard journal format over viewing the first 5 weeks of lab work

Course Outcomes and Assessment:

The outcomes below are assessed primarily through lab assignments and oral presentations.

A) An ability to apply knowledge of mathematics, science, and engineering

B) An ability to design and conduct experiments, as well as to analyze and interpret data

C) An ability to design a system, component, or process to meet desired needs

E) An ability to identify, formulate, and solve engineering problems

G) An ability to communicate effectively

K) An ability to use the techniques, skills, and modern engineering tools necessary for engineering practice (i.e. Computers and analytical equipment)

L) An understanding of biology and physiology

M) The capability to apply advanced mathematics (including differential equations and statistics), science, and engineering to solve the problems at the interface of engineering and biology

Relationship of course to departmental Program Educational Objectives:

These objectives are addressed through the lab assignments and group projects. See above course objectives.

  1. Pursue educational opportunities and/or employment in bioengineering-related fields, such as medicine, device development, or biotechnology.
  2. Contribute to responsible development of new technical knowledge.

Course grading:

4 Lab Progress Reports plus one Final Reports
1 Project (488: Paper; 588: Paper and Presentation)
1 Literature Review Paper Presentation

  • Lab Reports: 30%
  • Project: 50%
  • Participation: 10%
  • Literature Review: 10%

Course schedule by week/topic:

Week Date Lecture Lab
1 M 9/24 Protein Structure Intro to Sequence, Structure, and Homology Modeling with MODELLER
W 9/26 Homology Modeling and Introduction to Lab
2 M 10/1 Force Fields and Molecular Mechanics Intuitive Design, Rosetta Design
W 10/3 David Baker – Rosetta: Methods and Examples
3 M 10/8 Molecular Dynamics MD Simulations: WT full, RD full, WT fragment, designed fragment
W 10/10 Rules for Design I
4 M 10/15 Rules for Design II MD Analysis, Generation II Design and Simulation
W 10/17 Mike Regnier – Modulation of Calcium Binding in Cardiac Muscle
5 M 10/22 Design Examples I Generation II Analysis, Final Writeup
W 10/24 Design Examples II
6 M 10/29 Gabriele Varani – Designing RNA-Protein Interactions Final Lab Writeups Due
Start Project
W 10/31 Design Examples III
7 M 11/5 Literature Review Work on Project
W 11/7 Literature Review
8 M 11/12 Holiday – No Class Work on Your Project
W 11/14 Design Examples IV
9 M 11/19 Roland Strong – Vaccine Design Work on Your Project
W 11/21 No Class – Lab
10 M 11/26 Jonathan Cheng – Biosensor Design Keep Working on Your Project
W 11/28 Wendy Thomas – Design of New Adhesives
11 M 12/3 Presentations Work Really Hard on Your Project
W 12/5 Presentations
Wed 12/12 Project Writeups: Writeups due before Wed 12/12 at 5 pm

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