Simulation of NMR data reveals that proteins' local structures are stabilized by electronic polarization

Yan Tong, Chang G. Ji, Ye Mei, John Zhang

Research output: Contribution to journalArticle

Abstract

Molecular dynamics simulations of NMR backbone relaxation order parameters have been carried out to investigate the polarization effect on the protein's local structure and dynamics for five benchmark proteins (bovine pancreatic trypsin inhibitor, immunoglobulin-binding domain (B1) of streptococcal protein G, bovine apo-calbindin D9K, human interleukin-4 R88Q mutant, and hen egg white lysozyme). In order to isolate the polarization effect from other interaction effects, our study employed both the standard AMBER force field (AMBER03) and polarized protein-specific charges (PPCs) in the MD simulations. The simulated order parameters, employing both the standard nonpolarizable and polarized force fields, are directly compared with experimental data. Our results show that residue-specific order parameters at some specific loop and turn regions are significantly underestimated by the MD simulations using the standard AMBER force field, indicating hyperflexibility of these local structures. Detailed analysis of the structures and dynamic motions of individual residues reveals that the hyperflexibility of these local structures is largely related to the breaking or weakening of relevant hydrogen bonds. In contrast, the agreement with the experimental results is significantly improved and more stable local structures are observed in the MD simulations using the polarized force field. The comparison between theory and experiment provides convincing evidence that intraprotein hydrogen bonds in these regions are stabilized by electronic polarization, which is critical to the dynamical stability of these local structures in proteins.

Original languageEnglish (US)
Pages (from-to)8636-8641
Number of pages6
JournalJournal of the American Chemical Society
Volume131
Issue number24
DOIs
StatePublished - Jun 24 2009

Fingerprint

Nuclear magnetic resonance
Polarization
Proteins
Hydrogen
Hydrogen bonds
S100 Calcium Binding Protein G
Benchmarking
Egg White
Aprotinin
Molecular Dynamics Simulation
Muramidase
Interleukin-4
Molecular dynamics
Immunoglobulins
Enzymes
Computer simulation
Experiments

ASJC Scopus subject areas

  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry
  • Chemistry(all)

Cite this

Simulation of NMR data reveals that proteins' local structures are stabilized by electronic polarization. / Tong, Yan; Ji, Chang G.; Mei, Ye; Zhang, John.

In: Journal of the American Chemical Society, Vol. 131, No. 24, 24.06.2009, p. 8636-8641.

Research output: Contribution to journalArticle

@article{56a8e0814a5e47deb2d506d709ee8533,
title = "Simulation of NMR data reveals that proteins' local structures are stabilized by electronic polarization",
abstract = "Molecular dynamics simulations of NMR backbone relaxation order parameters have been carried out to investigate the polarization effect on the protein's local structure and dynamics for five benchmark proteins (bovine pancreatic trypsin inhibitor, immunoglobulin-binding domain (B1) of streptococcal protein G, bovine apo-calbindin D9K, human interleukin-4 R88Q mutant, and hen egg white lysozyme). In order to isolate the polarization effect from other interaction effects, our study employed both the standard AMBER force field (AMBER03) and polarized protein-specific charges (PPCs) in the MD simulations. The simulated order parameters, employing both the standard nonpolarizable and polarized force fields, are directly compared with experimental data. Our results show that residue-specific order parameters at some specific loop and turn regions are significantly underestimated by the MD simulations using the standard AMBER force field, indicating hyperflexibility of these local structures. Detailed analysis of the structures and dynamic motions of individual residues reveals that the hyperflexibility of these local structures is largely related to the breaking or weakening of relevant hydrogen bonds. In contrast, the agreement with the experimental results is significantly improved and more stable local structures are observed in the MD simulations using the polarized force field. The comparison between theory and experiment provides convincing evidence that intraprotein hydrogen bonds in these regions are stabilized by electronic polarization, which is critical to the dynamical stability of these local structures in proteins.",
author = "Yan Tong and Ji, {Chang G.} and Ye Mei and John Zhang",
year = "2009",
month = "6",
day = "24",
doi = "10.1021/ja901650r",
language = "English (US)",
volume = "131",
pages = "8636--8641",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "24",

}

TY - JOUR

T1 - Simulation of NMR data reveals that proteins' local structures are stabilized by electronic polarization

AU - Tong, Yan

AU - Ji, Chang G.

AU - Mei, Ye

AU - Zhang, John

PY - 2009/6/24

Y1 - 2009/6/24

N2 - Molecular dynamics simulations of NMR backbone relaxation order parameters have been carried out to investigate the polarization effect on the protein's local structure and dynamics for five benchmark proteins (bovine pancreatic trypsin inhibitor, immunoglobulin-binding domain (B1) of streptococcal protein G, bovine apo-calbindin D9K, human interleukin-4 R88Q mutant, and hen egg white lysozyme). In order to isolate the polarization effect from other interaction effects, our study employed both the standard AMBER force field (AMBER03) and polarized protein-specific charges (PPCs) in the MD simulations. The simulated order parameters, employing both the standard nonpolarizable and polarized force fields, are directly compared with experimental data. Our results show that residue-specific order parameters at some specific loop and turn regions are significantly underestimated by the MD simulations using the standard AMBER force field, indicating hyperflexibility of these local structures. Detailed analysis of the structures and dynamic motions of individual residues reveals that the hyperflexibility of these local structures is largely related to the breaking or weakening of relevant hydrogen bonds. In contrast, the agreement with the experimental results is significantly improved and more stable local structures are observed in the MD simulations using the polarized force field. The comparison between theory and experiment provides convincing evidence that intraprotein hydrogen bonds in these regions are stabilized by electronic polarization, which is critical to the dynamical stability of these local structures in proteins.

AB - Molecular dynamics simulations of NMR backbone relaxation order parameters have been carried out to investigate the polarization effect on the protein's local structure and dynamics for five benchmark proteins (bovine pancreatic trypsin inhibitor, immunoglobulin-binding domain (B1) of streptococcal protein G, bovine apo-calbindin D9K, human interleukin-4 R88Q mutant, and hen egg white lysozyme). In order to isolate the polarization effect from other interaction effects, our study employed both the standard AMBER force field (AMBER03) and polarized protein-specific charges (PPCs) in the MD simulations. The simulated order parameters, employing both the standard nonpolarizable and polarized force fields, are directly compared with experimental data. Our results show that residue-specific order parameters at some specific loop and turn regions are significantly underestimated by the MD simulations using the standard AMBER force field, indicating hyperflexibility of these local structures. Detailed analysis of the structures and dynamic motions of individual residues reveals that the hyperflexibility of these local structures is largely related to the breaking or weakening of relevant hydrogen bonds. In contrast, the agreement with the experimental results is significantly improved and more stable local structures are observed in the MD simulations using the polarized force field. The comparison between theory and experiment provides convincing evidence that intraprotein hydrogen bonds in these regions are stabilized by electronic polarization, which is critical to the dynamical stability of these local structures in proteins.

UR - http://www.scopus.com/inward/record.url?scp=67650551442&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650551442&partnerID=8YFLogxK

U2 - 10.1021/ja901650r

DO - 10.1021/ja901650r

M3 - Article

C2 - 19485377

AN - SCOPUS:67650551442

VL - 131

SP - 8636

EP - 8641

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 24

ER -