PROTEIN DESIGN

While the Folding@home, is striving to understand how existing proteins attain their specific, functional three-dimensional structures, the goal of Genome@home is to design new genes that can form working proteins in the cell. This is almost a reverse folding process.

In recent years, computational protein design methods have advanced to the point where significant questions regarding the relationship between protein sequence, structure, and function can be addressed.

We begin with a 3 Dimensional protein backbone structure.

BBA5 protein

The 3 dimensional structure of protein depends on sequence of amino acids the sequence of which is based on genetic code. However, different amino acid sequences could generate a similar 3 dimensional structure. Our goal is to find all the possible sequences (called sequence space)

We then try to match amino acid sequence with genetic code that would produce such a sequence. Finally search human genome database to match that genetic code.

We hope this process will lead into:

engineering new proteins for medical therapy
designing new pharmaceuticals
assigning functions to the dozens of new genes being sequenced every day
understanding protein evolution

To do this, researchers have turned to computers for help in predicting protein structure from gene sequences, a concept called homology modeling. The complete genomes of various organisms, including humans, have now been decoded and allow researchers to approach this goal in a logical and organized fashion.As you can imagine this process is very computation intensive beyond the computation power of even super computers. We use distributed computing through genome@home .

A computer-generated image of a protein's structure shows the relative locations of most, if not all, of the protein's thousands of atoms. The image also reveals the physical and chemical properties of the protein and provides clues about its role in the body. See for example CHICKEN VILLIN HEADPIECE

It is theorized that proteins that share a similar sequence generally share the same basic structure. Therefore, by experimentally determining the structure for one member of a protein family, called a target, researchers have a model on which to base the structure of other proteins within that family. Moving a step further, by selecting a target from each superfamily, researchers can study the universe of protein folds in a systematic fashion and outline a set of sequences associated with each folding motif. Many of these sequences may not demonstrate a resemblance to one another, but their identification and assignment to a particular fold is essential for predicting future protein structures using homology modeling.

The scientific basis for these theories is that a strong conservation of protein three-dimensional shape across large evolutionary distances—both within single species, between species, and in spite of sequence variation—has been demonstrated again and again. Although most scientists choose high-priority structures as their targets, this theory provides the option to choose any one of the proteins within a family as the target, rather than trying to achieve experimental results using a protein that is particularly difficult to work with using crystallographic or NMR techniques.

Web Author: Tug Sezen