Bio357 Protein Design Fall, 2002

Sharpless 217 Robert Fairman

WF 2:30-4:00

Introduction

In this course, we will survey topics in experimental and computational protein design and do some protein design work ourselves focusing on coiled coils, using our SGI workstations in the new computer cluster (INSC, H205B). The beginnings of the field of protein design can be traced back principally to work started in the early 1980's. This field owes its beginnings largely to the pioneers who worked out many of the basic rules that define protein folding and stability. The two people, working independently, who first developed the concepts in protein design are Jane Richardson and William DeGrado. We will focus on their work early in this course as an acknowledgement of their contribution to this field. After this historical introduction to the literature, we will focus on more recent papers that introduce additional design approaches, particularly computational approaches, followed by attempts to introduce functionality. For example, we might look at attempts to design metal binding, heme binding, catalytic function into proteins, and perhaps even explore the use of proteins in nanoscience and biomaterial design. While studying important papers on design, we will also be introducing and discussing the most important biophysical and molecular biological techniques used in protein chemistry as background information to help understand the experimental work.

To help you access the literature for this course, a web page has been constructed with all the articles attached as links or pdf’s. You’ll find the web page at the following link:

http://trires.brynmawr.edu/coursepage.asp?cid=551

I’ll provide the password for this course page at the first meeting.

Requirements

The format that we will use to discuss the articles will be for pairs of students to present papers assigned for a particular date. I will work with each pair of students in preparing for their presentations and, depending on your particular paper, will assist in presenting this paper, principally by introducing the background needed to understand the paper. I will judge several factors in presentations. These will include (1) in-depth understanding of the paper; (2) analysis of the presentation of the data; (3) critical assessment of the interpretation of the data and conclusions drawn by the authors; (4) and presentation style and ability to engage the class in discussion. Everyone is expected to read the assigned papers prior to class and be prepared to discuss them. Your engagement in this discussion will be a major part of your grade!.

In addition to the assigned reading, we will have three exercises in protein design taking advantage of our SGI workstation. The exercises will be discussed in detail in class and you will be working closely with me to complete these exercises.

The grading for this course will be broken down as follows:

Presentations: 40%

Participation: 20%

SGI exercises 40%

Syllabus

Date	Lecture/project discussion	Paper
Sep. 4	Review of torsion angles and rotamer concepts	Rotamer reviews 1 and 2
6	Biophysical techniques in protein structure and design, part I	BYOJA
11	Biophysical techniques in protein structure and design, part II	BYOJA
13	Understanding energy functions and using InsightII. (review: Pokala & Handel, 2001)	Online Tutorial.
18	Design of coiled-coil structures (review: Hill et al., 2000) Due Date for Exercise #1	Ho & DeGrado, 1987 Hill & DeGrado, 2000
20	Functionalization: metal-binding (review: Kennedy & Gibney, 2001)	Handel et al., 1993 Marsh & DeGrado, 2002
25	X-ray crystallographic approaches.	Harbury et al., 1993 Harbury et al., 1998
27	Parameterization of coiled coils towards class projects.	North et al., 2001
Oct. 2	Computational approaches. (review: Kraemer-pecore et al., 2001) Due Date for Exercise #2	Desjarlais & Handel, 1995 Hellinga & Richards, 1994
4	Catalytic design approaches	Yao et al., 1997 Isaac et al., 2002
9	Combinatorial approaches (review: Saven, 2002)	Finucane et al., 1999 Wang & Hecht, 2002
11	Self-assembling polymers (Yeates & Padilla, 2002)	Padilla et al., 2001
23	Design of beta-sheet proteins	Mayo et al., 1996 (ref.) Venkatraman et al., 2002
25	Wrap-up of final project. Due Date for Exercise #3