Solvation Thermodynamics of Oligoglycine with Respect to Chain Length and Flexibility

Justin A. Drake, Robert C. Harris, Bernard Pettitt

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Oligoglycine is a backbone mimic for all proteins and is prevalent in the sequences of intrinsically disordered proteins. We have computed the absolute chemical potential of glycine oligomers at infinite dilution by simulation with the CHARMM36 and Amber ff12SB force fields. We performed a thermodynamic decomposition of the solvation free energy (ΔGsol) of Gly2–5 into enthalpic (ΔHsol) and entropic (ΔSsol) components as well as their van der Waals and electrostatic contributions. Gly2–5 was either constrained to a rigid/extended conformation or allowed to be completely flexible during simulations to assess the effects of flexibility on these thermodynamic quantities. For both rigid and flexible oligoglycine models, the decrease in ΔGsol with chain length is enthalpically driven with only weak entropic compensation. However, the apparent rates of decrease of ΔGsol, ΔHsol, ΔSsol, and their elec and vdw components differ for the rigid and flexible models. Thus, we find solvation entropy does not drive aggregation for this system and may not explain the collapse of long oligoglycines. Additionally, both force fields yield very similar thermodynamic scaling relationships with respect to chain length despite both force fields generating different conformational ensembles of various oligoglycine chains.

Original languageEnglish (US)
Pages (from-to)756-767
Number of pages12
JournalBiophysical Journal
Volume111
Issue number4
DOIs
StatePublished - Aug 23 2016

Fingerprint

Thermodynamics
Intrinsically Disordered Proteins
Amber
Entropy
Static Electricity
Glycine
Proteins

ASJC Scopus subject areas

  • Biophysics

Cite this

Solvation Thermodynamics of Oligoglycine with Respect to Chain Length and Flexibility. / Drake, Justin A.; Harris, Robert C.; Pettitt, Bernard.

In: Biophysical Journal, Vol. 111, No. 4, 23.08.2016, p. 756-767.

Research output: Contribution to journalArticle

Drake, Justin A. ; Harris, Robert C. ; Pettitt, Bernard. / Solvation Thermodynamics of Oligoglycine with Respect to Chain Length and Flexibility. In: Biophysical Journal. 2016 ; Vol. 111, No. 4. pp. 756-767.
@article{060df41924e04697afc09692bcc17f4f,
title = "Solvation Thermodynamics of Oligoglycine with Respect to Chain Length and Flexibility",
abstract = "Oligoglycine is a backbone mimic for all proteins and is prevalent in the sequences of intrinsically disordered proteins. We have computed the absolute chemical potential of glycine oligomers at infinite dilution by simulation with the CHARMM36 and Amber ff12SB force fields. We performed a thermodynamic decomposition of the solvation free energy (ΔGsol) of Gly2–5 into enthalpic (ΔHsol) and entropic (ΔSsol) components as well as their van der Waals and electrostatic contributions. Gly2–5 was either constrained to a rigid/extended conformation or allowed to be completely flexible during simulations to assess the effects of flexibility on these thermodynamic quantities. For both rigid and flexible oligoglycine models, the decrease in ΔGsol with chain length is enthalpically driven with only weak entropic compensation. However, the apparent rates of decrease of ΔGsol, ΔHsol, ΔSsol, and their elec and vdw components differ for the rigid and flexible models. Thus, we find solvation entropy does not drive aggregation for this system and may not explain the collapse of long oligoglycines. Additionally, both force fields yield very similar thermodynamic scaling relationships with respect to chain length despite both force fields generating different conformational ensembles of various oligoglycine chains.",
author = "Drake, {Justin A.} and Harris, {Robert C.} and Bernard Pettitt",
year = "2016",
month = "8",
day = "23",
doi = "10.1016/j.bpj.2016.07.013",
language = "English (US)",
volume = "111",
pages = "756--767",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "4",

}

TY - JOUR

T1 - Solvation Thermodynamics of Oligoglycine with Respect to Chain Length and Flexibility

AU - Drake, Justin A.

AU - Harris, Robert C.

AU - Pettitt, Bernard

PY - 2016/8/23

Y1 - 2016/8/23

N2 - Oligoglycine is a backbone mimic for all proteins and is prevalent in the sequences of intrinsically disordered proteins. We have computed the absolute chemical potential of glycine oligomers at infinite dilution by simulation with the CHARMM36 and Amber ff12SB force fields. We performed a thermodynamic decomposition of the solvation free energy (ΔGsol) of Gly2–5 into enthalpic (ΔHsol) and entropic (ΔSsol) components as well as their van der Waals and electrostatic contributions. Gly2–5 was either constrained to a rigid/extended conformation or allowed to be completely flexible during simulations to assess the effects of flexibility on these thermodynamic quantities. For both rigid and flexible oligoglycine models, the decrease in ΔGsol with chain length is enthalpically driven with only weak entropic compensation. However, the apparent rates of decrease of ΔGsol, ΔHsol, ΔSsol, and their elec and vdw components differ for the rigid and flexible models. Thus, we find solvation entropy does not drive aggregation for this system and may not explain the collapse of long oligoglycines. Additionally, both force fields yield very similar thermodynamic scaling relationships with respect to chain length despite both force fields generating different conformational ensembles of various oligoglycine chains.

AB - Oligoglycine is a backbone mimic for all proteins and is prevalent in the sequences of intrinsically disordered proteins. We have computed the absolute chemical potential of glycine oligomers at infinite dilution by simulation with the CHARMM36 and Amber ff12SB force fields. We performed a thermodynamic decomposition of the solvation free energy (ΔGsol) of Gly2–5 into enthalpic (ΔHsol) and entropic (ΔSsol) components as well as their van der Waals and electrostatic contributions. Gly2–5 was either constrained to a rigid/extended conformation or allowed to be completely flexible during simulations to assess the effects of flexibility on these thermodynamic quantities. For both rigid and flexible oligoglycine models, the decrease in ΔGsol with chain length is enthalpically driven with only weak entropic compensation. However, the apparent rates of decrease of ΔGsol, ΔHsol, ΔSsol, and their elec and vdw components differ for the rigid and flexible models. Thus, we find solvation entropy does not drive aggregation for this system and may not explain the collapse of long oligoglycines. Additionally, both force fields yield very similar thermodynamic scaling relationships with respect to chain length despite both force fields generating different conformational ensembles of various oligoglycine chains.

UR - http://www.scopus.com/inward/record.url?scp=84991736551&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991736551&partnerID=8YFLogxK

U2 - 10.1016/j.bpj.2016.07.013

DO - 10.1016/j.bpj.2016.07.013

M3 - Article

VL - 111

SP - 756

EP - 767

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 4

ER -