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Importance of sequence specificity for predicting protein folding pathways: Perturbed Gaussian chain model
Author(s) -
Kameda Tomoshi
Publication year - 2003
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.10427
Subject(s) - topology (electrical circuits) , protein folding , sequence (biology) , folding (dsp implementation) , protein sequencing , computational biology , chain (unit) , gaussian network model , gaussian , protein structure , peptide sequence , chemistry , physics , biology , mathematics , computational chemistry , gene , biochemistry , combinatorics , astronomy , electrical engineering , engineering
Recent experimental and theoretical studies suggest that rates and pathways of protein folding are largely decided by topology of the native structures, at least for small proteins. However, some exceptions are known; for example, protein L and protein G have the same topology, but exhibit different characteristics of the TSE. Thus, folding pathways of some proteins are critically affected by detailed information on amino acid sequences. To investigate the sequence specificity, we calculate folding pathways of 20 small proteins using the perturbed Gaussian chain model developed by Portman et al. (Phys Rev Lett 1998;81:5237–5240; J Chem Phys 2001;114:5069–5081). Characteristics of the TSE predicted by the model are in good agreement with experimental ϕ‐value data for many proteins at coarse‐grained level. Especially, estimation of folding TSE for protein G and protein L based on both topology and additional sequence information are consistent with experimental ϕ‐value data. With only topology information, however, the model predicts the TSE of protein G incorrectly. Moreover, the model that uses topology and sequence information describes free energy profiles of two‐state and three‐state folders consistently with experiment, whereas the topology only model predicts free energy profiles of some proteins incorrectly. This indicates that sequence specificity also has critical roles in determining the folding pathways for some proteins. Proteins 2003. © 2003 Wiley‐Liss, Inc.