Knowledge-based Protein Re-engineering

Efforts in protein reengineering are motivated by two goals: developing novel molecular reagents that expand and improve the function of natural proteins, and testing our fundamental understanding of how proteins fold and function. Creative Biolabs is dedicated to establishing the most exquisite service platform for our clients and our one-stop protein engineering services can provide comprehensive technical support to advance our clients' projects.

Introduction to Knowledge-based Protein Re-engineering

The core problem of protein reengineering is the construction of an energy function that describes protein stability. Nearly all scoring energy functions utilize empirical information learned from protein sequence, structure, and function databases to either improve the calculation of site-specific energies or drastically reduce the combinatorial complexity of inter-residue interactions. In re-engineering algorithms, sequences that minimize the potential function are expected to have the greatest likelihood of adopting the target structure. Knowledge-based protein reengineering can be abstractly defined as the attempt to use information from the distribution of natural proteins to identify new, non-natural sequences that encode desired target regions in the structure and function databases.

Knowledge-based protein re-engineering: information from sequence databases

Sequence alignments have typically been used to study the evolutionary constraint of sites in a protein family, a parameter given by the distribution of amino acids allowed at each position. By postulating that this constraint reflects the physical chemistry underlying protein structure and function, many studies have attempted to use the pattern of conservation in reengineering proteins.

Knowledge-based protein re-engineering: information from structural databases

Knowledge-based potentials derived from secondary and tertiary structures of proteins comprise key elements of nearly every protein re-engineering algorithm. Structure-based knowledge potentials include rotamer libraries derived from known protein structures; binary patterning; an implicit solvation model; secondary structure propensity; and libraries correlating backbone structures with small segments of protein sequences in the Protein Data Bank. A key aspect of successfully applying knowledge-based potentials has been an empirical adjustment of the parameters of the energy function to achieve the best correlation of computed and experimentally observed properties of the designed sequences.

Knowledge-based protein re-engineering potentials: information from functional databases

Databases that correlate functional variation with sequence and/or structure variations can significantly aid reengineer efforts by targeting sequence variation to specific determinants of protein function. A major goal in protein re-engineering is the rational design of functional properties such as binding specificity, allosteric regulation, and catalysis. Scientists have introduced a Ca²⁺-binding site into a non-Ca²⁺-binding protein. The key is the computational survey of naturally occurring Ca²⁺-binding motifs in the context of their target protein to identify a Ca²⁺-binding site that is structurally and chemically compatible with both Ca²⁺ binding and the surrounding protein environment.

Fig.1 Schematic representation of the protein sequence-structure-function.

Services

The knowledge-based approach provides a short cut to rational protein re-engineering by predictive site-specific potentials learned from databases of protein structures and sequences. A particular sequence adopts a native state ensemble in the structure databases (protein folding), which then displays a particular biochemical activity (structure-function). Therefore, we can provide various knowledge-based protein re-engineering services from three databases (sequences, structures, and functions) to meet customers' specific requirements.

Creative Biolabs has been involved in the field of protein engineering for many years and we are committed to completing your project with high quality. We have accumulated a wealth of scientific experience from our completed projects and provide you with the best services to ensure your requirements are met. If you are interested in our services, please contact us for more details.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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