Variations in chain compactness and topological complexity uncover foldingprocesses in the relaxation dynamics of unfolded in vacuo lysozyme

Chain collapse and the formation of a near-native tertiary structure are be lieved to be two key features controlling the progress of a protein folding transition. In this work, we study the interrelation between these two pro perties along computer-simulated relaxation trajectories of unfolded in vac uo lysozyme. Large-scale molecular shape transitions are monitored within a space defined by two discriminating descriptors of chain compactness and e ntanglement (or "topological") complexity. For the system studied here, res ults indicate that successful refolding into native-like conformers require s a balance between polymer collapse and a topologically "correct" organiza tion of chain loops. Although no single factor dominates the relaxation pat hs, compactization appears to be a necessary condition for near-native refo lding. Whenever initial collapse is limited or absent, we find a "derailed" folding path with high configurational frustration. We also show that disu lfide-reduced lysozyme unfolds differently, yet relaxes to the pattern of m olecular shapes characteristic of the folded states of disulfide-intact lys ozyme. (C) 1999 American Institute of Physics. [S0021-9606(99)50634-X].