Criterion that Determines the Foldability of Proteins

Abstract

We show, using lattice models of proteins, how the kinetic accessibility of the native state of proteins is encoded in the primary sequence itself. The folding times for various sequences correlate extremely well with the single parameter intrinsic to the sequence, namely, $\ensuremath{\sigma}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}|{T}_{\ensuremath{\theta}}{\ensuremath{-}T}_{f}|{/T}_{\ensuremath{\theta}}$ where ${T}_{\ensuremath{\theta}}$ and ${T}_{f}$ are the collapse and folding transition temperatures. Fast folding sequences have small values of $\ensuremath{\sigma}$ (typically less than 0.1) whereas $\ensuremath{\sigma}$ values for slow folding sequences exceed 0.6. The folding times change by 5 orders of magnitude when $\ensuremath{\sigma}$ goes from 0.05 to a value exceeding about 0.6.