My name is Charles Craik.
I'm a professor at the University of California San Francisco.
I'm going to be speaking to you on the fundamentals and principles
for engineering proteolytic activity.
What is protein engineering?
It is the creation of new proteins.
The field of protein engineering began in earnest
during the early 1980s with the advent of site directed mutagenesis.
This powerful new tool provided protein chemists and
structural biologists with the ability to alter proteins in a predictable fashion,
much in the same way that an engineer can alter his or her surroundings.
The techniques for engineering proteins that are predominantly recombinantly based,
are established and readily available in various kits from numerous inventors.
So I will focus my talk on the applications of protein engineering.
What are some of the goals of protein engineering?
Well, one of them is to understand structure-function relationships of proteins.
Using protein engineering, you can surgically dissect
the relationship between the structure and the function of a protein.
Also, you can use protein engineering to create proteins with novel properties.
And finally, to define the fundamental roles of de novo protein design,
pretty much the holy grail of protein engineering.
Now, these are lofty goals.
However, looking back at approximately 25 years of protein engineering,
one thing can be stated for certain,
and that is to expect the unexpected.
One way to visualize this is shown on the following slide.
In the lower left-hand corner you see a small tomato.
To its right, is a large tomato.
You can imagine trying to engineer the small one into the large one.
To draw the analogy to proteins,
you can imagine on the left-hand side would be your preexisting protein
and on the right is the protein you'd like to engineer it into,
with novel unique properties.
However, you sometimes get the unexpected.
In the case of protein engineering,
that is when you want to analyze those variants,
and as I will bring up elsewhere in the rest of the talk,
that is frequently where deep insight can result.
Now, that is not to say that significant accomplishments have not already been achieved.