189

Protein Structure Analysis

It is not uncommon that the basic type of protein structure is already known. Then you can

get the three-dimensional structure coordinates from the protein database and then use a

protein visualization program to insert the mutations that you would like to plan.

We have already got to know RasMol as a visualization program and the PDB database

for the three-dimensional protein structure coordinates.

For proteins that have similarity to a protein sequence, we can make a homology model

(see Sect. 1.2), for example with SWISS-MODEL or MODELLER. Again, remember to

be conscientious about comparing original sequence and modification.

Prediction of the New Protein Properties

Next, one considers how the protein then changes overall. Various methods for mutation

prediction exist, e.g. large protein alignments of related proteins enable the comparison of

correlated mutations to identify even distant regions that influence each other in coopera­

tive structural changes (e.g. working group of Prof. Ranganathan). This method is

described in detail in Poelwijk et al. (2016). A case study investigates how allostery and

protein structures can be specifically changed using this method (Raman et al. 2016).

A nice, simple start-up software package to plan molecular biology experiments is the

Geneious software or the Husar software at DKFZ. Both software packages allow a lot of

molecular biology for new proteins and the individual steps for this: the planning and

recognition of DNA interfaces for cloning experiments, the prediction of secondary struc­

ture, amino acid composition, optimal protein expression, translation of nucleotide

sequences, protein modification, etc. (we have already used the Expert Analysis System as

a general introduction). (As a general introduction, we already got to know the Expert

Protein Analysis System (ExPASy) from Switzerland in Part I).

https://www.geneious.com/

https://genius.embnet.dkfz-­heidelberg.de/menu/biounit/tools_db.shtml

https://fold.it/portal/info/science

More ambitious protein design experiments are building on this. The current world

leader is David Baker’s lab at the Institute for Protein Design (Institut für Protein-Design)

at the University of Washington (Universität Washington; https://www.ipd.uw.edu). A nice

introduction is the game “Fold it” (first link below), the second link below gives a com­

plete overview of modern protein design.

13.8  Using the Language of Life Technically with the Help of Synthetic Biology