Protein Design from Scratch: De Novo Protein Design via MultiParameter Functional Constraint Integration

Abstract

A novel computational framework for de novo protein design that prioritizes biological function over traditional structural modeling. By integrating specific biophysical and biochemical constraints—such as molecular weight, pH, and hydrophobicity—the system directly generates a primary amino acid sequence capable of performing complex tasks. This method incorporates diverse functional modules, including kinase and signaling domains, to streamline the creation of high-performing biomolecules without the need for extensive folding simulations. To demonstrate the framework's effectiveness, the author successfully engineered a synthetic glucokinase that exhibits precise binding affinity and catalytic flexibility. Ultimately, this parameter-to-sequence paradigm offers a faster, more resource-efficient path toward discovering innovative therapeutic enzymes and industrial biocatalysts. Tool Link: https://proprint-seq-designer.lovable.app/