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Relative stability of de novo four–helix bundle proteins: Insights from coarse grained molecular simulations
Author(s) -
Bellesia Giovanni,
Jewett Andrew I.,
Shea Joan–Emma
Publication year - 2011
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.605
Subject(s) - helix bundle , bundle , sequence (biology) , helix (gastropod) , molecular dynamics , stability (learning theory) , protein structure , amino acid residue , protein design , computational biology , peptide sequence , crystallography , chemistry , physics , biophysics , biology , computer science , genetics , materials science , computational chemistry , biochemistry , gene , ecology , machine learning , snail , composite material
Abstract We use a recently developed coarse‐grained computational model to investigate the relative stability of two different sets of de novo designed four–helix bundle proteins. Our simulations suggest a possible explanation for the experimentally observed increase in stability of the four–helix bundles with increasing sequence length. In details, we show that both short subsequences composed only by polar residues and additional nonpolar residues inserted, via different point mutations in ad hoc positions, seem to play a significant role in stabilizing the four–helix bundle conformation in the longer sequences. Finally, we propose an additional mutation that rescues a short amino acid sequence that would otherwise adopt a compact misfolded state. Our work suggests that simple computational models can be used as a complementary tool in the design process of de novo proteins.