Protein Design. Week 3

Part A: Protein Analysis

Questions:



Protein

For this exercise we were asked to pick any protein (from any organism) that has a 3D structure and answer the following questions:

Again I faced a huge problem in choosing one protein.

I think Circadian Clock proteins are very inspiring. I was thinking of choosing one of them.

After all I chose...

1BET

1Bet is a protein which is a nerv growth factor protein. The organism was mouse (mus musculus). It was added in 1993. After that time more similar proteins where mapped.

This protein belongs to the family of Neurotrophins, which guide the development of the nervous system.

Brain is composed of 85 billion interconnected neurons. Individually, each neuron receives signals from its many neighbors, and based on these signals, decides whether to dispatch its own signal to other nerve cells. Together, the combined action of all of these neurons allows us to sense the surrounding world, think about what we see, and make appropriate actions. Remarkably, this complicated structure is formed in nine short months as an embryo grows into a baby. Nerve cells start as typical, compact cells, but then they send out long axons and dendrites, connecting to other cells in the brain or even to entirely different parts of the body. Neurons in the growing brain test the connections with their neighbors, looking for the proper wiring. Half of the neurons are discarded during this process, in areas that get too crowded. The half that remain become the nervous system. Throughout the rest of life, these neurons typically do not reproduce, although they do send out more dendrites to neighboring cells as the nervous system grows or repairs damaged areas.

Hint: Use the pBLAST tool to search for homologs and ClustalOmega to align and visualize them.

Structure page RCSB of mine protein

cartoon
with atoms

ball and sticks
surface solid
cartoon

Color the protein by secondary structure. Does it have more  helices or  sheets?

(Chimera)

If blue is hydrophilic and red hydrophobic it seem that they are rather evenly distributed.

It also seem like it has more sheets than helices.

Links:


Rubisco (http://pdb101.rcsb.org/motm/11)

PDB pioneers (http://pdb101.rcsb.org/search)


Part B: How to (almost) Fold (almost) Anything - Protein Folding

In this part you will be folding protein sequences into 3D structures. The goal is to get an understanding on how computational protein modeling works as well as to see first hand the great computing power needed for molecular simulations in biology.

Folded Structure of the enzyme PEThase made in Robetta

3D Printed protein (unfortunately part of it was damaged during printing)


Part C: Protein Design by Machine Learning