Freezing Transition of Heteropolymers

The ability to create synthetic heteropolymers with the protein-like capabilities of renaturation to a particular conformation capable of specific molecular recognition is of great technological importance. To create protein-like heteropolymers, we suggest "Imprinting," which dictates that monomers should be equilibrated at some low temperature prior to polymerization, then polymerized such that this monomer prearrangement is somewhat preserved. We argue that this optimization of monomers to themselves and to the target molecule prior to polymerization leads respectively to the protein-like properties of stability and functionality since the prearrangement of monomers is analogous to optimization performed by nature over evolutionary time. Thus, many of our results are applicable to proteins and may shed light on their biological and prebiological origins. To study Imprinting, we employ a variety of theoretical techniques. Since we must prove that the single heteropolymer conformation capable of specific molecular recognition dominates equilibrium, to computationally study the thermodynamics of Imprinted heteropolymers, we must enumerate every possible globular conformation; using a massively parallel supercomputer, we found the conformations in which the chains were polymerized were indeed the lowest energy conformation. We also validated Imprinting by the Monte Carlo kinetics of lattice models, thereby showing that the chains we proved to have the lowest energy conformations were able to kinetically access this conformation. Finally, we used replica mean field theory to examine the relationship between the nature of interactions chosen and the success of Imprinting by calculating the phase behavior for Imprinted heteropolymers directly from the microscopic Hamiltonian of monomer-monomer interactions; we have theoretically shown that Imprinting is feasible and indeed robust with respect to variations in several aspects, including the chemistry employed, interactions of monomers in the soup versus on the polymer, and the target molecule intended for recognition. Thesis Supervisor: Toyoichi Tanaka Title: Professor of Physics