ProPHECY™ – in silico Protein and Peptide Optimization
Modifying and optimizing the amino acid sequence of a protein or peptide enables the creation of a model to understand its quantitative structure-activity relationships (QSAR).
ProPHECY™ – in silico Protein and Peptide Optimization
ProPHECY™ in silico protein and peptide optimization can be used in biotechnology and the design of biological drugs. Modifying and optimizing the amino acid sequence of a protein or a peptide allows for the creation of a model to understand its quantitative structure-activity relationships (QSAR). This knowledge can then be used to control and modify reactivity and other properties. Our software package, ProPHECY™, works similarly to the well-known QSAR methodology used in small molecule drug design.
QSAR optimization
The ProPHECY™ ProPHECY™ in silico protein and peptide optimization software package is designed for QSAR-analysis of protein modifications. It uses a unique algorithm that leverages experimentally determined protein parameters to predict amino acid replacements needed to create new protein or peptide variants. The algorithm analyzes large and complex data sets to uncover hidden information and provides detailed quantitative insights into how each amino acid replacement influences the protein. Additionally, it can simultaneously optimize multiple parameters.
- biological or catalytic activity
- antigenicity (decrease or increase)
- enhancement of cell-penetrating capabilities
- protease resistance
- thermal stability
- solubility, etc.
This method significantly reduces the time, effort, and costs needed for protein and peptide optimization compared to traditional random screening. Contact us to discuss your project!
Related publications on the use of ProPHECY™ in silico protein and peptide optimization
Pasupuleti, M. Walse, B., Svensson, B., Malmsten, M. and Schmidtchenet, A. (2008). Rational design of antimicrobial C3a analogs with enhanced effects against Staphylococci using an integrated structure and function-based approach.
Biochemistry, 47, 9057-9070.
The anaphylatoxin C3a and its inactivated form C3adesArg, which are produced when the complement system is activated, have direct antimicrobial effects through their C-terminal region. Over time, this region of C3a has undergone subtle changes in its overall electrical charge, while maintaining a moderate but varying level of amphipathicity. In this research, the authors imitate these evolutionary changes by making specific amino acid substitutions at key positions in the original human C3a peptide CNYITELRRQHARASHLGLA, followed by studies to determine the structure-activity relationship (QSAR) of these new peptide variants of C3a, in order to enhance their effects.
Kassetty, G. Papareddy, P., Kalle, M., Rydengård, V., Walse, B., Svensson, B., Mörgelin, M., Malmsten, M. and Schmidtchen, A. (2011). The C-terminal sequence of several human serine proteases encodes host defense functions.
J Innate Immun, 3, 471-482.
Serine proteases of the S1 family have maintained a common structure for over one billion years of evolution. They have developed a variety of specificities for different substances and have diverse biological roles, such as digestion, blood clotting, fibrinolysis, and maintaining the balance in the epithelium. Our research shows that many C-terminal peptide sequences of serine proteases, especially from the coagulation and kallikrein systems, share similarities with classical antimicrobial peptides of innate immunity. These peptides have antimicrobial effects and also modulate the immune response by inhibiting macrophage reactions to bacterial lipopolysaccharides under normal conditions.
