Polarization of intraprotein hydrogen bond is critical to thermal stability of short helix

Ya Gao, Xiaoliang Lu, Li L. Duan, John Zhang, Ye Mei

Research output: Contribution to journalArticle

Abstract

Simulation result for protein folding/unfolding is highly dependent on the accuracy of the force field employed. Even for the simplest structure of protein such as a short helix, simulations using the existing force fields often fail to produce the correct structural/thermodynamic properties of the protein. Recent research indicated that lack of polarization is at least partially responsible for the failure to successfully fold a short helix. In this work, we develop a simple formula-based atomic charge polarization model for intraprotein (backbone) hydrogen bonding based on the existing AMBER force field to study the thermal stability of a short helix (2I9M) by replica exchange molecular dynamics simulation. By comparison of the simulation results with those obtained by employing the standard AMBER03 force field, the formula-based atomic charge polarization model gave the helix melting curve in close agreement with the NMR experiment. However, in simulations using the standard AMBER force field, the helix was thermally unstable at the temperature of the NMR experiment, with a melting temperature almost below the freezing point. The difference in observed thermal stability from these two simulations is the effect of backbone intraprotein polarization, which was included in the formula-based atomic charge polarization model. The polarization of backbone hydrogen bonding thus plays a critical role in the thermal stability of helix or more general protein structures.

Original languageEnglish (US)
Pages (from-to)549-554
Number of pages6
JournalJournal of Physical Chemistry B
Volume116
Issue number1
DOIs
StatePublished - Jan 12 2012

Fingerprint

helices
Hydrogen bonds
Thermodynamic stability
thermal stability
field theory (physics)
Polarization
hydrogen bonds
polarization
proteins
simulation
Proteins
Nuclear magnetic resonance
melting
Protein folding
nuclear magnetic resonance
hydrogen
replicas
Freezing
folding
melting points

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Materials Chemistry
  • Surfaces, Coatings and Films

Cite this

Polarization of intraprotein hydrogen bond is critical to thermal stability of short helix. / Gao, Ya; Lu, Xiaoliang; Duan, Li L.; Zhang, John; Mei, Ye.

In: Journal of Physical Chemistry B, Vol. 116, No. 1, 12.01.2012, p. 549-554.

Research output: Contribution to journalArticle

Gao, Ya ; Lu, Xiaoliang ; Duan, Li L. ; Zhang, John ; Mei, Ye. / Polarization of intraprotein hydrogen bond is critical to thermal stability of short helix. In: Journal of Physical Chemistry B. 2012 ; Vol. 116, No. 1. pp. 549-554.
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