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212015.0 Protein structure

in Bioscience 4 sp (PSB)

Tiina Salminen, PhD, title of Docent (tiina.salminen@abo.fi)

Senior lecturer in structural biochemistry and bioinformatics

Structural Bioinformatics Laboratory, BioCity 3rd A floor

(www.abo.fi/fak/mnf/bkf/research/sbl)

Department of Biosciences

Åbo Akademi University



Pirkko Heikinheimo, PhD, title of Docent

University of Turku & University of Helsinki

Courses at Structural Bioinformatics

Laboratory (SBL)

  Applied bioinformatics, comparative modeling, computer-

aided drug design

  Applied Bioinformatics 8 sp

  282001.0 Computer in Bioresearch (Applied Bioinformatics I) 2 sp:

  Introduction to our computer system

  www- course in Moodle

  282002.0 Applied Bioinformatics 6 sp:

  282003.0 Molecular modeling 4 sp

  2010-2011: Protein structure in bioscience

  283002.0 Structure-based drug design, 4 sp

  2010-2011: Computer aided drug design

  Course language is English but Swedish can be used in the

exam and project report

  Dictionaries allowed and language is not taken into account

in grading

212015.0 Protein structure in Bioscience 4 sp

  Sign-up Online:-17.01.2011:

  Instructions on www-page: https://www.abo.fi/student/coursesbiosci

  First register and then login with the e-mailed password

  You must have an ÅA Student number to get your credits:

  Fill in the Electronic JOO application (www.joopas.fi)

  Sign-up for the exercises open after 18.1.2011 in Moodle

  Do you have BioCity Magnetic Key?

  The key can be programmed to allow access to this department

  If you have an access to this department the time limit can be extended to

21.00 o’clock

  If you wish that your key will be activated, please, contact me after this

lecture

212015.0 Protein Structure in Bioscience 4 sp

•  Lectures (10 h)

•  Computer exercises (10 h)

•  Quiz (short exam): Amino acids & Terminology and principles of protein

structure (in the beginning of the 2ndsTutorial) – Material in Moodle

•  Exam: 2-4 course exam dates:

  1. Exam: 4.3 Friday 10.15-12.00

  2. Exam 11.3 Friday 10.15-12.00

•  Project work + report (10 h)

–  will be done in pairs at your own time





Grade : ~ Quiz 10%+ Exam 70% + Project 20%

Literature

  Course material in Moodle: http://moodle2.vasa.abo.fi/

  BIOVET – Biovetenskap - Protein structure in bioscience

  Moodle enrollment key: PSB2011



  Course language is English

  You may contact me in English, Swedish or Finnish

  Exam/project can be done in English or Swedish

Literature

  Liljas, A., Liljas, L., Piskur, J., Lindblom, G., Nissen, P.,

Kjeldgaard, M. (2009) Textbook Of Structural Biology

  Xiong, J. (2006) Essential Bioinformatics

  Höltje, H.-D., Sippl, W., Rognan, D., and Folkers, G. (2003)

Molecular Modeling. Basic Principles and Applications.

(Second edition); 3rd edition 2008

212015.0 Protein Structure in Bioscience

Lectures: Week 6

  7.2 Monday:13.15-15.00 Aud Biokemi

  Introduction

  Quiz material: Terminology and Principles of protein structure





  8.2 Tuesday:10.15-12.00 Aud Biokemi

  3D Structure determination methods



  9.2 Wednesday: 13.15-15.00 Aud Biokemi

  Sequence alignment; Bodil presentation

  Introduction to computer exercises

212015.0 Protein Structure in Bioscience

Computer exercises Obligatory!

  Computer room, Biochemistry and Pharmacy, ÅA, BioCity 3rd floor

  15 Linux/(Windows dual boot) workstations

  Will be done alone or in pairs

  Project work relies on the computer exercises!

  5 Tutorials (1,2,3,4,5) – 3 groups (A,B,C=TERBIO, D)

  Exercise 1:Searching and saving protein structure

  Exercise 2:Quiz & Pymol: a program to visualise protein structures

  Exercise 3: Analysis and comparison of enzymes structures: serine proteases

  Exercise 4:Analysis and comparison of receptors structures: integrins

  Exercise 5:Alpha-mannosidose mutant

Computer exercises







  Sign-up in Moodle

  Group C is available ONLY for University of Turku Health Bioscience students (TerBio).

  Group D is designed for University of Turku Bioinformatics students (Note dates!)

  15 places (18 in group C) available/exercise

  Preferentially, choose the same group for all tutorials but you may choose a different group as

well!

212015.0 Protein Structure in Bioscience

Lectures: Week7

  14.2 Monday:13.15-15.00 Aud Biokemi

  Alpha-mannosidases



  15.2 Tuesday: 10.15-12.00 Aud Biokemi

  Integrins

Exam

  You may choose one of the course exam dates

  Sign-up in Moodle



Week 9

  4.3 Friday 10.15-12.00 1. Exam Aud Biokemi

Week 10

  11.3 Friday 10.15-12.00 2. Exam Aud Biokemi

  3rd exam? Suggestions?

Projects – select in Moodle

  Based on protein structures and related articles

  Project submitted in Moodle

  At your own time

  Preferably in pairs (can be done alone)

  Project descriptions in Moodle

  Information in Moodle

  You may work with your own protein of interest!

  Send an email and tell about the protein

Week12

  21.3 Monday Dead line for PROJECT REPORTS

Grade : ~ Quiz 10%+ Exam 70% + Project 20%

Projects – select in Moodle

  Protein-Protein Interaction   Inhibiting the Enzyme

  Integrin Activity

  Growth Hormone Receptor   Cyclooxygenase-1

  Haemoglobin   HMG-CoA reductase

  Type 5 phosphodiesterase

  Protein-Ligand interaction   Dihydrofolate reductase

  α2A -adrenergic receptor   β-lactamase

  β2 adrenergic receptor   HIV protease

  β1-adrenergic receptor   HIV reverse transcriptase

(pdb 1FK9)



  Disease causing mutations   Own project?

Projects – select in Moodle

  E.g. Protein-Protein Interaction:

Integrin (PDB ID 3HI5, 3HI6)

  Explain conformational changes upon ligand binding

  Search for the structures from the protein structure database (PDB)

  Search for the related article

  Explain the desired details:

  With figures (prepared with Pymol) and figure text

  Supporting text: Introduction, Results, Concluding remarks, References

  Focus on the requested data – you cannot explain everything!

  Ask for help if you have a problem

  21.2. and 22.2 in computer room (group D)

  By email

Project report in a poster form

  Use the example layout

  Make the project report in a A4

poster form according to the

example (left) in Moodle

Why structural biology?

  ”In order to understand, we need to see.”

  “Seeing is believing.”

  James Watson 1964:

  “Unfortunately, we cannot accurately describe at the

chemical level how a molecule functions unless we first

know its structure”

Why protein structures?

  Proteins have key functional roles needed for life

  Function by specific recognition of other molecules

  Recognition leads to changes (shape, chemistry,

interactions) that lead to functional effects

  Enzymes, receptors, hormones, transport proteins,

immunoglobulin, structural protein, motor proteins,

signaling proteins, storage proteins

Structures are valuable in interpreting

sequence-structure-function relationship

  Find out the requirements for protein folding, stability,

dynamics and function

  Predict the function of a protein

  Explain the effect of polymorphism or other mutations

  Establish new or modify old function e.g.

  Increase stability (e.g.. thermostability in washing powders )

  Modified enzymes in chemical processes

  Analyze interactions

  Protein –ligand interactions

  Drug design – develop new compounds that bind to protein

  Protein – protein interactions in biological processes

  Explain the results from experimental studies

  Design new experiments to test predictions

After this course the student:

  is familiar with protein 3D structures, comparison and superposition of

3D structures, protein evolution, sequence alignment and sequence-

structure-function relationship

  can critically utilize scientific literature and data deposited on protein

3D structures

  knows how to relate published data on protein structures to its biological

function

  can formulate a project report on the performed task



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