Protein Modeling, Lecture 4


Last week we learned how to complete a protein structure that has missing structural information by fitting, 'cutting and pasting' a piece from an identical protein with its corresponding secondary structure configuration, or by simply adding missing amino acids to the gaps without any secondary structure features.

This week we will quickly do the same to insulin, but we will go a little further.

We are going to add enterokinase to insulin, and join the insulin structure to that of Leucine-zipper by a couple of Glycine-Serine linkers. We will merge these two proteins so that their chain identifiers, and amino acid sequence numbers are correct from the N-terminal of insulin, to the C-terminal of the added leucine zipper protein.

There are some intermediate steps in this process that will require the use of the programs reduce and CHARMM, which are installed in your docker image, just as an introduction step in which you learn how to run the scripts, but you do not need to write the scripts.

I expect that in this lecture you will be more comfortable navigating the docker image environment, so the typing of the commands is done more efficiently. And that will probably give us time to move ahead after joining insulin and leucine zipper.

I will start introducing the methodology for evaluating the conformational sampling of new linker designs in order to evaluate protein constructs to make insulin. Conformational sampling? what the heck!. Don't worry, I will introduce the first few basic theoretical concepts in protein simulations, and you will use the program to make a dandelion kind of construct.

As always, visualization in VMD is the last step.

FIY: I had a video conference with another bio-hacker group in Europe last Friday. I explained to them what I am doing with this lectures and the open insulin project, and they are interested in collaborating!