Why Sequence Blockiness Sharpens Coil–Globule Transition in Heteropolymers

Coil–globule transition in a single-chain polymer is the cornerstone of polymer physics. Although completely understood for homopolymers, it turns out to be much more sophisticated for copolymers of mere two nonionic monomers because the position and especially sharpness (cooperativity) of the conformational change in them are highly sequence-dependent. In this work, the statistical theory of coil–globule transition in neutral AB copolymers with regular sequences is developed. To describe the role of the primary structure, we go beyond the mean-field approximation and calculate the Gaussian fluctuation correction due to chemical differences (incompatibility) between A and B monomers. Local compositional fluctuations reduce the second and third virial coefficients of monomer interactions; these corrections are found in the general form, and closed-form expressions are provided for block-alternating chains with the block length m. For nonperiodic sequences, the found corrections are annealed averages. Increasing the monomer blockiness is shown to (i) make the globule denser, (ii) shift the conformational transition to higher temperatures, and, most importantly, (iii) narrow the transition region. The collapse sharpens strongly when accompanied or shortly followed by intraglobular microphase separation. The developed theory contributes to a comprehensive understanding of the sequence-tunable conformational behavior of macromolecules, including Khokhlov–Khalatur protein-like copolymers forming globules with the core–shell microstructure.