Premium
Molecular dynamics study on folding and allostery in RfaH
Author(s) -
Xiong Liqin,
Liu Zhenxing
Publication year - 2015
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.24839
Subject(s) - allosteric regulation , cooperativity , molecular dynamics , ctd , chemistry , helix (gastropod) , folding (dsp implementation) , crystallography , biophysics , protein folding , biochemistry , biology , computational chemistry , ecology , oceanography , engineering , snail , electrical engineering , enzyme , geology
ABSTRACT Upon being released from the N‐terminal domain (NTD), the C‐terminal domain (CTD) switches from α ‐helix conformation to β ‐barrel conformation, which converts RfaH from a transcription factor into an activator of translation. The α → β conformational change may be viewed as allosteric transition. We use molecular dynamics simulations of coarse‐grained off‐lattice model to study the thermal folding of NTD, CTD, RfaH and the allosteric transition in CTD. The melting temperatures from the specific heat profiles indicate that the β ‐barrel conformation is much more stable than the α ‐helix conformation. Two helices in α ‐helix conformation have similar thermodynamic stabilities and the melting temperatures for β sheets show slight dispersion. Under the interaction with NTD, CTD is greatly stabilized and the cooperativity for thermal folding is also significantly improved. The α → β allosteric transition can be approximately described by a two‐state model and three parallel pathways are identified. The transition state ensemble, quantified by a Tanford β ‐like parameter, resembles the α ‐helix and β ‐barrel conformations almost to the same extent. Proteins 2015; 83:1582–1592. © 2015 Wiley Periodicals, Inc.