Why Sequence\nBlockiness Sharpens Coil–Globule\nTransition in Heteropolymers

Coil–globule transition in a single-chain polymer\nis the\ncornerstone of polymer physics. Although completely understood for\nhomopolymers, it turns out to be much more sophisticated for copolymers\nof mere two nonionic monomers because the position and especially\nsharpness (cooperativity) of the conformational change in them are\nhighly sequence-dependent. In this work, the statistical theory of\ncoil–globule transition in neutral AB copolymers with regular\nsequences is developed. To describe the role of the primary structure,\nwe go beyond the mean-field approximation and calculate the Gaussian\nfluctuation correction due to chemical differences (incompatibility)\nbetween A and B monomers. Local compositional fluctuations reduce\nthe second and third virial coefficients of monomer interactions;\nthese corrections are found in the general form, and closed-form expressions\nare provided for block-alternating chains with the block length <i>m</i>. For nonperiodic sequences, the found corrections are\nannealed averages. Increasing the monomer blockiness is shown to (i)\nmake the globule denser, (ii) shift the conformational transition\nto higher temperatures, and, most importantly, (iii) narrow the transition\nregion. The collapse sharpens strongly when accompanied or shortly\nfollowed by intraglobular microphase separation. The developed theory\ncontributes to a comprehensive understanding of the sequence-tunable\nconformational behavior of macromolecules, including Khokhlov–Khalatur\nprotein-like copolymers forming globules with the core–shell\nmicrostructure.