It is well accepted that a protein’s sequence encoded by DNA is the key foundation toward its structure and functions. Extensive efforts have been devoted to synthesis of sequence-specific synthetic polymers (oligomers and multi-block copolymers) and to probe how the changes in monomer sequence affect the polymer behavior. However, it remains as a question: “what extent of sequence specificity is needed in synthetic polymers to exhibit protein-like behavior?†Recent experimental studies demonstrated that random heteropolymers (RHPs) with statistical sequence control could be designed to recapitulate proteins’ functions. This is orthogonal to well accepted protein sequence-structure-function approaches in biology. The proposed studies aim to answer an important question on what these RHPs are at different levels ranging from segment, single-chain, to clusters in solution. Systematic studies from the angle of polymer phase behavior will combine the fountain of knowledge in traditional polymer science and biology. Successful RHP developments may enable polymers to molecularly interface with biological processes and ultimately lead to hybrid functional materials.
The project includes broad interdisciplinary educational and mentoring aspects, outreach, development of undergraduate laboratory modules, as well as creation of publicly available software tools for RHP sequence simulation and analysis to overcome the initial barriers in RHP design.
PART 2: TECHNICAL SUMMARY
RHPs act as chaperon proteins to stabilize enzymes in non-native environments and channel proteins to selectively, rapidly transport protons. Recently results on such RHPs suggested that monomeric sequence specificity is not the prerequisite to replicate some properties of natural proteins. It is feasible to rationally design RHPs with protein-like behavior. This project will experimentally study the RHPs’ synthesis and solution behavior at the single-chain level and as ensembles and provide experimental foundation toward initial understanding of this class of complex, challenging, and useful polymeric materials. Specifically, the planned studies focus on: (1) Synthesis and characterization of RHP libraries with controlled composition and statistical monomer distribution; (2)Phase behavior of RHPs in dilute solutions; (3) Assemblies of RHPs in solutions with increased concentration. In parallel, the PI's group will synthesize and characterize model block copolymers to delineate effects of statistical monomer distribution in RHPs.
As an orthogonal approach to sequence-specific polymers, RHPs represent a rarely explored area in terms of polymer design and encompass controlled randomness as a critical design parameter. If successful, the planned studies will pave the path toward truly protein-like polymers synthetically. With the interdisciplinary nature of RHP approach,these studies provide a platform to promote polymer science among different scientific communities and training opportunities for the next generation of materials scientists. The project includes broad interdisciplinary educational and mentoring aspects, outreach, development of undergraduate laboratory modules, as well as creation of publicly available software tools for RHP sequence simulation and analysis to overcome the initial barriers in RHP design. .
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
