ProPHECY™ – in silico Protein and Peptide Optimization
The ProPHECY™ in silico protein optimization software package is designed for quantitative structure-activity relationship (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.
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 peptide enables 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™, operates similarly to the well-known QSAR methodology used in small-molecule drug design.
ProPHECY™ in silico protein and peptide optimization: Case studies
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 yet variable level of amphipathicity. In this research, the authors simulate these evolutionary changes by making specific amino acid substitutions at key positions in the original human C3a peptide, CNYITELRRQHARASHLGLA, and then conduct studies to determine the structure-activity relationship (SAR) of these new C3a peptide variants 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 play diverse biological roles, such as digestion, blood clotting, fibrinolysis, and maintaining epithelial balance. Our research reveals that many C-terminal peptide sequences of serine proteases, particularly those from the coagulation and kallikrein systems, exhibit similarities with classical antimicrobial peptides of innate immunity. These peptides exhibit antimicrobial activity and modulate the immune response by inhibiting macrophage responses to bacterial lipopolysaccharides under normal conditions.
