Rational Heteropolymer Design Based on Protein Sequence Space

In contrary to well accepted protein sequence-structure-function relationship, random heteropolymers (RHPs) embrace controlled randomness as a critical design parameter to access protein-link behaviors. We hypothesize that proteins' segmental sequence information can guide statistic sequence control in RHPs to holistically replicate protein functions. I will discuss our recent efforts to translate protein sequence information into RHP design. Specifically, we extracted the chemical characteristics and sequential arrangement along a protein chain from natural protein libraries and used the information to design heteropolymer ensembles as protein mimics. Experimentally, the level of segmental similarity to that of natural proteins determines its ability to replicate proteins' multiple functions. Molecular studies further translated protein sequence information at the segmental level into intermolecular interactions with a defined range, degree of diversity, and temporal and spatial availability. This framework provides valuable guiding principles to synthetically realize protein properties, engineer bio/abiotic hybrid materials, and ultimately, realize matter-to-life transformations.