Core-Shell Model of Folding-Unfolding Transitions (UFT) in Proteins

There are $\sim $10$^{N}$ conformations for a protein of length $N$ to sort out randomly in search of lowest free energy state. Can protein folding be simple and fast? Core-shell model introduces principles, proposes mechanisms and scores residues of fast, reversible UFT in protein. According to it, during UFT the realm of intra-residual interactions leads the residue motion. The scaffold of hydrophilic residues forms external shell of unstructured, tube-like protein in unfolded state, just as the hydrophobic residues form internal scaffold -- core, of the protein in folded state. As UFT proceeds, residue slides into lowest-score position permitted by its structure. Model accounts for experimentally observed features of UFT. It is based on three principles: 1) During UFT protein is \textit{virtual} - its features or structure are inferred only statistically and with limited precision; 2) Mechanism of UFT memory is not longitudinal, but \textit{transverse}; 3) Native design overrides specific features of residues - the alphabet of amino acids assumes an \textit{intrinsic} score-function. Per-residue mechanism of UFT is proposed and score-function is described. Difference graphs of transitional score-function and average genome-wide abundance index show that our score-function \textit{is} the order parameter of UFT in protein and by virtue of being it, reveals transitional key residues. It echoes the multiple-tier and funnel concepts of FEL perspective. Monte Carlo simulations of UFT in myoglobin illustrate the idea.