TY - JOUR
T1 - Transient, highly populated, building blocks folding model
AU - Tsai, Chung Jung
AU - Nussinov, Ruth
N1 - Funding Information:
We thank Drs. Buyong Ma, Sandeep Kumar, and particularly Jacob V. Maizel for many helpful discussions. The research of R. N. in Israel has been supported in part by grant number 95-00208 from the BSF, by the Center of Excellence administered by the Israel Academy of Sciences, by the Magnet grant, by a Ministry of Science grant, and by the Tel Aviv University Basic Research and Adams Brain Center grants. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number NO1-CO-56000. The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. government.
PY - 2001
Y1 - 2001
N2 - Protein folding is a hierarchical event, in which transiently formed local structural elements assemble to yield the native conformation. In principle, multiple paths glide down the energy landscape, but, in practice, only a few of the paths are highly traveled. Here, the literature is reviewed in this light, and, particularly, a hierarchical, building block protein-folding model is presented, putting it in the context of a broad range of experimental and theoretical results published over the past few years. The model is based on two premises: First, although the local building block elements may be unstable, they nevertheless have higher population times than all alternate conformations; and, second, protein folding progresses through a combinatorial assembly of these elements. Through the binding of the most favorable building block conformers, there is a redistribution of the conformers in solution, propagating the protein-folding reaction. We describe the algorithm, and illustrate its usefulness, then we focus on its utility in assigning simple vs complex folding pathways, on chaperonin-assisted folding, on its relevance to domain-swapping processes, and on its relevance and relationship to disconnectivity graphs and tree diagrams. Considering protein folding as initiating from local transient structural elements is consistent with available experimental and theoretical results. Here, we have shown that, early in the folding process, sequential interactions are likely to take place, even if the final native fold is a complex, nonsequential one. Such a route is favorable kinetically and entiopically. Through the construction of anatomy trees, the model enables derivation of the major folding pathways and their bumps, and qualitatively explains the kinetics of protein folding.
AB - Protein folding is a hierarchical event, in which transiently formed local structural elements assemble to yield the native conformation. In principle, multiple paths glide down the energy landscape, but, in practice, only a few of the paths are highly traveled. Here, the literature is reviewed in this light, and, particularly, a hierarchical, building block protein-folding model is presented, putting it in the context of a broad range of experimental and theoretical results published over the past few years. The model is based on two premises: First, although the local building block elements may be unstable, they nevertheless have higher population times than all alternate conformations; and, second, protein folding progresses through a combinatorial assembly of these elements. Through the binding of the most favorable building block conformers, there is a redistribution of the conformers in solution, propagating the protein-folding reaction. We describe the algorithm, and illustrate its usefulness, then we focus on its utility in assigning simple vs complex folding pathways, on chaperonin-assisted folding, on its relevance to domain-swapping processes, and on its relevance and relationship to disconnectivity graphs and tree diagrams. Considering protein folding as initiating from local transient structural elements is consistent with available experimental and theoretical results. Here, we have shown that, early in the folding process, sequential interactions are likely to take place, even if the final native fold is a complex, nonsequential one. Such a route is favorable kinetically and entiopically. Through the construction of anatomy trees, the model enables derivation of the major folding pathways and their bumps, and qualitatively explains the kinetics of protein folding.
KW - Building block
KW - Disconnectivity graphs
KW - Funnels
KW - Misfolding
KW - Protein folding
KW - Sequential folding
UR - http://www.scopus.com/inward/record.url?scp=0035750382&partnerID=8YFLogxK
U2 - 10.1385/CBB:34:2:209
DO - 10.1385/CBB:34:2:209
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AN - SCOPUS:0035750382
VL - 34
SP - 209
EP - 235
JO - Cell Biochemistry and Biophysics
JF - Cell Biochemistry and Biophysics
SN - 1085-9195
IS - 2
ER -