Sullivan Normal Office 2004 Test Drive User 2 2007-01-31T22:57:00Z 2007-09-20T14:24:00Z 2007-09-20T14:24:00Z 1 817 4657 Biology 38 9 5719 11.773 96 800x600

BME 225 –

Protein Function in Biology and Bioinformatics

 

Please direct any enquiries to Dietlind Gerloff (gerloff@soe.ucsc.edu; 9x4833; PSB320)

Notes (Oct 29, 2007):

  • GUEST LECTURE Tue Oct 30 in PSB305:
    Protein-Protein Interactions
    Seth Rubin (Dept of Chemistry & Biomedical Sciences)
  • Protein Function Journal Club (BME281G) is meeting at a different time on Friday this week:
    Fri Nov 2, 2p in PSB305 - check out the BME281G www-page for more details.
  • Email (fast) availability to discuss your ideas re your projects: Tue Oct 30, 4-6p (gerloff@soe.ucsc.edu)

 

Course description

 

Course reviewing functional roles of proteins and computational methods used to predict functional aspects of proteins. The primary focus will be on molecular function (catalysis of biochemical reactions; physical interactions with DNA, RNA, or other proteins; ion channels etc.) and structure-function relationships.  Wider-reaching notions of function (pathways, interaction networks) will be considered peripherally, as the context in which molecular function occurs. The course will include lectures, (computational) lab work, and discussions of topical publications. Prerequisite(s):  Biochemistry 100A or higher (or equivalent knowledge) and/or Chemistry 200B; BME205B and BME220B are recommended but not required. Enrollment is restricted to graduate students; students not satisfying the prerequisite requirement may seek instructor's permission to enroll with additional reading assignments.

 

Course times and location

 

TUE 2-3:45p and THU 1-2:45p - Class room: PSB305 (Physical Sciences Building)

 

Lecture Topics and Slides:

As the course progresses, I will keep a list of the topics we discussed here.

A list with suggested predicton servers and/or methods to investigate during your BME225 research assignment can be found here (posted Oct 16).

 

 

(Provisional) Overall Course Outline and Structure

 

The course will generally involve one taught session (lecture) and one applied/practical session (computational lab exercises; paper discussions; student presentations) per week.

The course is loosely structured in a biological part (overviewing the diversity of natural protein function on behalf of examples, and the wetlab methods used for functional characterization) and a bioinformatics part (reviewing current strategies and methods to predict function).

An overview of due dates for assignments etc (as discussed briefly in class during week 1) can be found here.

The topics tenatively scheduled for each week are:

 

Week 1: Protein function – general overview and classification schemes

By comparison to protein structure the term "protein function" is far less well defined. Researchers will use the term vaguely and differently depending on their background and interests. What schemes are there to sub-classify the wide variety of functions carried out by proteins in their natural environment -  what are their strengths and weaknesses?

 

Week 2 + 3: Enzymes

The best understood type of molecular function is catalysis of a biochemical reaction.  We also know the 3D-structures of many enzymes. Can we understand their mechanisms (better) by looking at these structures – are there commonalities that may be useful for predicting enzyme function? 

 

Week 4: DNA/RNA-protein interactions

Interactions between proteins and DNA and/or RNA are crucial to all transcriptional regulation. Best understood and characterized are specific interactions, e.g. recognition of a promoter sequence by a transcription factor. Additionally there are a variety of more "generic" DNA/RNA-binding events that are of great importance, e.g. for discarding unwanted RNA molecules etc. Do 3D-structures provide enough information to  "break the recognition code"â How much constraint is imposed onto evolutionary sequence variation by this type of function?

 

Week 5 + 6: Protein-protein interactions

Due to an (even) greater variety in shape and physicochemical properties in protein partners, the diversity in protein-protein interactions is almost ungraspable (for us bioinformaticians). Issues to consider and discuss here are: transient versus permanent interactions, conformational changes (including those triggered by post-translational modifications) , specific versus unspecific interactions.  Where may lie clues for prediction methods basing on sequence and/or structure?

 

Week 7: Other functions and consideration of a wider context

There are many other types of protein function that may be considered variations or combinations of the types discussed previously, or not. Our knowledge of molecular protein function is generally limited to "well-behaved" proteins, i.e. those adopting well-defined 3D-structures, typically at a minimum energy state. What other proteins are there and are their functions not also molecular in nature? What clues toward protein function can be gained by proteomic (experimental high-throughput) methods?

 

Week 8-10: Computational methods for function prediction

Where these have not been mentioned during the previous weeks, a selection of existing computational strategies to tackle protein function prediction will be reviewed and discussed. Why is prediction of function so difficult? This part of the course will include student presentations and discussions guided by the instructor.

 

Evaluation (revised Oct 4, 2007)

 

Students will be evaluated based on their performance on

 

1. Two homework assignments (20% each)

2. An individual project involving literature and WWW/computational research, evaluated based on a summary report/paper* (max 10 pages; research to be carried out before Week 8) (40%)

3. A presentation of the project results to the class (10%)

4. Participation in class (10%)

*: Note that students involved in thesis/rotation research are not required to submit a written project report but can opt