Tuning the globular assembly of hydrophobic/hydrophilic heteropolymer sequences

We propose a heteropolymer design scheme to tune monomer distributions that stabilize or destabilize the collapsed globular conformation relative to random sequencing. Polymer sequences trained via globular templating are mapped to a one-dimensional Ising-like model, and inverse Monte Carlo simulations are performed to determine an effective interaction between monomers that reproduces intrasequence correlations. Heteropolymer sequences generated using this effective interaction quantitatively reproduce the coil-to-globule transition with increasing polymer hydrophobicity observed for templated sequences. Through potential scaling, the range of transition hydrophobic fractions required to collapse the polymer opens up by a factor of 2, from a minimum fraction of 17% to a maximum of 32% for the longest polymers simulated. Collapsed conformations are favored by sequences in which there is intermediate segregation of hydrophobic and hydrophilic units along the backbone, while monomer integration favors coils.