Extras

The question

This course is all about "Being lazy", or "A month in the lab can easily save you an hour in front of the computer". Further, we cannot experiment on humans, but we can (if really needed and ethically OK) experiment on mice, and we can experiment freely on yeast and bacilli. The location and type of function are most conserved.

The tools

MRS, BLAST, CLUSTAL, YASARA. These were the tools of the course. Not because they are without competition, but because they are very good, nice for education, and representative for all we do in molecular bioinformatics.

Amino acids

BLAST and CLUSTAL compare sequences (needed because we normally cannot compare structures). They do that by ligning up amino acids. This principally cannot always go well. Therefore we need to understand the amino acids, and knowing their characteristics (all of them) is guaranteed going to be part of the exam. Hydrophobicity (expressed as entropy of water) is by far the most important characteristic of amino acids.

Structure

The role of amino acids is influenced by the (secondary) structure they are in. There is a relation between sequence and (secondary) structure. Anfinsen. Secondary structure: helix, strand, turn. β-turn is special turn that, together with N-terminal side of the helix, is well recognizable in the sequence. Helix, turn, and strand have characteristics that are expressed in the residue composition and distribution.

Sequences don't exist, structures do.

Whenever you see a sequence, please remember that it actually is a failed picture of a structure. And if you make alignments, remember that you are not aligning sequences, but structures, so things must fit.

Knowledge gadgets.

There are a few commonly occurring acive sites: Ser-His-Asp, Asp-(Asp or Glu)-Asp, (His)_n-Zn, and a whole series of other ones that make up the rest. Active sites in enzymes tend to sit at or near the C-terminal side of β-strands. Residues stick out of strands and helices in a special way that, when you know it, helps you understand the sequence-structure relations.

Summary

When it is conserved it is important, and when it is important, it stays conserved.

EU name: PERDAY

This page holds one or a few questions about the 'previous' day in the course. We will start every day with these questions, to make sure that the essentials of the previous day have been understood. As we will not always teach the course in whole-day blocks, the questions will not be sorted by day, but simply follow the flow of the course.

These 'control-questions' are also a good source for exam-questions...

The goal of the course

Question 123: What is the deepest, most abstract goal of this course? And what tools, techniques, and skills will you (need to) learn to achieve that overriding goal? And which software and data products are we going to use once you have those skills?

Software and databases

Question 124: What is good and what is bad about the SwissProt database?

Question 125: In this course we will use many databases occasionally, but three database very frequently. Which are those three database, and what kinds) of data do they each contain?

Question 126: In this course we will use many types of software, but four computer programs (of which three are available as a Web server, and one is on your hard disk) will be used more frequently. Which are those four programs, and what can you do with each of them?

Amino acids

Question 127: What is the overriding goal of this course? And how are we going to achieve that goal?

Question 128: Why do we need to know the characteristics of amino acids? And which characteristic is the most important one?

Question 129: Some amino acids are special (Pro is rigid, Gly is flexible, cys can form bridges, etc). Why is this important knowledge?

Structures

Question 130: Here some good overall question about structures. Help.

Secondary structure

Question 131: Lets go back one step. What was the overriding goal of this course again? And why do we need sequence alignments to achieve that goal? And why do we need to understand so much about the characteristics of amino acids to make those alignments?

Question 132: Why do we need to know anything about protein secondary structure if we actually are only interested in the transfer of information?