TY - JOUR
T1 - Thermodynamics of Conformational Transitions in a Disordered Protein Backbone Model
AU - Drake, Justin A.
AU - Pettitt, B. Montgomery
N1 - Publisher Copyright:
© 2018 Biophysical Society
PY - 2018/6/19
Y1 - 2018/6/19
N2 - Conformational entropy is expected to contribute significantly to the thermodynamics of structural transitions in intrinsically disordered proteins or regions in response to protein/ligand binding, posttranslational modifications, and environmental changes. We calculated the backbone (dihedral) conformational entropy of oligoglycine (GlyN), a protein backbone mimic and model intrinsically disordered region, as a function of chain length (N=3, 4, 5, 10, and 15) from simulations using three different approaches. The backbone conformational entropy scales linearly with chain length with a slope consistent with the entropy of folding of well-structured proteins. The entropic contributions of second-order dihedral correlations are predominantly through intraresidue ϕ-ψ pairs, suggesting that oligoglycine may be thermodynamically modeled as a system of independent glycine residues. We find the backbone conformational entropy to be largely independent of global structural parameters, like the end-to-end distance and radius of gyration. We introduce a framework referred to herein as “ensemble confinement” to estimate the loss (gain) of conformational free energy and its entropic component when individual residues are constrained to (released from) particular regions of the ϕ-ψ map. Quantitatively, we show that our protein backbone model resists ordering/folding with a significant, unfavorable ensemble confinement free energy because of the loss of a substantial portion of the absolute backbone entropy. Proteins can couple this free-energy reservoir to distal binding events as a regulatory mechanism to promote or suppress binding.
AB - Conformational entropy is expected to contribute significantly to the thermodynamics of structural transitions in intrinsically disordered proteins or regions in response to protein/ligand binding, posttranslational modifications, and environmental changes. We calculated the backbone (dihedral) conformational entropy of oligoglycine (GlyN), a protein backbone mimic and model intrinsically disordered region, as a function of chain length (N=3, 4, 5, 10, and 15) from simulations using three different approaches. The backbone conformational entropy scales linearly with chain length with a slope consistent with the entropy of folding of well-structured proteins. The entropic contributions of second-order dihedral correlations are predominantly through intraresidue ϕ-ψ pairs, suggesting that oligoglycine may be thermodynamically modeled as a system of independent glycine residues. We find the backbone conformational entropy to be largely independent of global structural parameters, like the end-to-end distance and radius of gyration. We introduce a framework referred to herein as “ensemble confinement” to estimate the loss (gain) of conformational free energy and its entropic component when individual residues are constrained to (released from) particular regions of the ϕ-ψ map. Quantitatively, we show that our protein backbone model resists ordering/folding with a significant, unfavorable ensemble confinement free energy because of the loss of a substantial portion of the absolute backbone entropy. Proteins can couple this free-energy reservoir to distal binding events as a regulatory mechanism to promote or suppress binding.
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U2 - 10.1016/j.bpj.2018.04.027
DO - 10.1016/j.bpj.2018.04.027
M3 - Article
C2 - 29925017
AN - SCOPUS:85048624847
SN - 0006-3495
VL - 114
SP - 2799
EP - 2810
JO - Biophysical journal
JF - Biophysical journal
IS - 12
ER -