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Metastability of protein native folds with respect to global variations in primary sequence
Author(s) -
Arteca Gustavo A.,
Veluri Kalyani
Publication year - 2002
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.10095
Subject(s) - metastability , protein folding , native state , chemical physics , chemistry , folding (dsp implementation) , sequence (biology) , crystallography , contact order , molecular dynamics , fold (higher order function) , translation (biology) , protein dynamics , computational chemistry , computer science , messenger rna , organic chemistry , electrical engineering , gene , engineering , biochemistry , programming language
In the absence of water, a range of rapid large‐scale conformational rearrangements is accessible in principle to a protein. Despite this, experiments and computer simulations suggest that native states need not be totally unstable once a protein is dehydrated. Here, we explore further the possibility that native folds act as conformational attractors in vacuo, despite variations on their primary structure. To this end, we carry molecular dynamics simulations on “protein chimeras,” where a protein sequence is threaded onto the backbone corresponding to the native state of a different protein with the same chain length. The simulations mimic the conditions of unrestricted rotation and translation found in gas‐phase or in vacuo experiments. We find that the chimeras show a range of motions commensurable to that of the original native state. In no case do we observe a complete change in folding features during early relaxation; in most cases, the original fold is actually metastable. The results suggest that the initial dynamical behavior of a protein may be dictated by the large‐scale backbone folding features, and not by details of the primary structure. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem 88: 220–225, 2002