BACKGROUND
A long-standing challenge within protein science and engineering is that different members of a protein family have functionally distinct properties. It is observable that two members of a protein family each have a property which is helpful for a specific application. For example, if one homolog can exhibit high thermal stability while another homolog has a high catalytic rate, it is industrially advantageous to be able to parse this structure-function variance within the protein family. Protein homologs often have substantially different amino acid sequences, resulting in a combinatorial explosion of different possible combinations of residue substitutions. However, there is no current method of determining which substitutions between homologs cause observable functional differences. As such, protein engineering, gene annotation, and protein research are obfuscated, creating complications and limitations to industrial, medical, and research abilities. There is a clear need for tools parsing the variance in the structure-function roles within protein families to control protein functionality.
SUMMARY OF TECHNOLOGY
Researchers at OSU have developed a novel method to identify specific residues of a protein family in order to achieve functional properties for engineering and research. More specifically, large availability of DNA sequences is leveraged to first identify homologs of a studied protein, and then this information is used to reconstruct all ancestral proteins that gave rise to the observed sequence variation in the protein family in question. Studying the biochemical properties of strategically selected ancestral proteins after their resurrection based on synthetic gene technology, substitutions are rapidly and effectively identified for specific functional differences. Thus, this novel approach provides a generalized but effectively implementable tool to address the challenge of combinatorial explosion of substitutions in identifying structure-function rules in protein families, enabling control over protein function and deepening the understanding of this critical class of biomolecules.
POTENTIAL AREAS OF APPLICATION
MAIN ADVANTAGES
STAGE OF DEVELOPMENT