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Exploring zipping and assembly as a protein folding principle
Author(s) -
Voelz Vincent A.,
Dill Ken A.
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21234
Subject(s) - sequence (biology) , chain (unit) , sequence space , space (punctuation) , folding (dsp implementation) , maxima and minima , order (exchange) , folding funnel , protein folding , closure (psychology) , polypeptide chain , contact order , nucleation , computer science , crystallography , physics , algorithm , chemistry , mathematics , pure mathematics , engineering , thermodynamics , downhill folding , banach space , mathematical analysis , operating system , biochemistry , phi value analysis , market economy , finance , astronomy , electrical engineering , economics , enzyme , nuclear magnetic resonance
It has been proposed that proteins fold by a process called “Zipping and Assembly” (Z&A). Zipping refers to the growth of local substructures within the chain, and assembly refers to the coming together of already‐formed pieces. Our interest here is in whether Z&A is a general method that can fold most of sequence space, to global minima, efficiently. Using the HP model, we can address this question by enumerating full conformation and sequence spaces. We find that Z&A reaches the global energy minimum native states, even though it searches only a very small fraction of conformational space, for most sequences in the full sequence space. We find that Z&A, a mechanism‐based search, is more efficient in our tests than the replica exchange search method. Folding efficiency is increased for chains having: (a) small loop‐closure steps, consistent with observations by Plaxco et al. 1998;277;985–994 that folding rates correlate with contact order, (b) neither too few nor too many nucleation sites per chain, and (c) assembly steps that do not occur too early in the folding process. We find that the efficiency increases with chain length, although our range of chain lengths is limited. We believe these insights may be useful for developing faster protein conformational search algorithms. Proteins 2007. © 2006 Wiley‐Liss, Inc.