Polarization of Intraprotein Hydrogen Bond Is Critical to Thermal Stability of Short Helix

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...

Full description

Saved in:
Bibliographic Details
Published in:The journal of physical chemistry. B 2012-01, Vol.116 (1), p.549-554
Main Authors: Gao, Ya, Lu, Xiaoliang, Duan, Li L, Zhang, John Z. H, Mei, Ye
Format: Article
Language:English
Subjects:
B: Biophysical Chemistry
Backbone
Charge
Computer simulation
Hydrogen Bonding
Magnetic Resonance Spectroscopy
Melting
Molecular Dynamics Simulation
Polarization
Protein Folding
Protein Structure, Secondary
Protein Unfolding
Proteins
Proteins - chemistry
Thermal stability
Thermodynamics
Transition Temperature
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1520-6106
1520-5207
DOI:10.1021/jp208953x