Ab initio Quantum Mechanics/Molecular Mechanics Molecular Dynamics Simulation of CO in the Heme Distal Pocket of Myoglobin

Xian Wei Wang, John Zhang, Xiao He

Research output: Contribution to journalArticle

Abstract

Myoglobin has important biological functions in storing and transporting small diatomic molecules in human body. Two possible orientations of carbon monoxide (CO) in the heme distal pocket (named as B1 and B2 states) of myoglobin have been experimentally indicated. In this study, ab initio quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulation of CO in myoglobin was carried out to investigate the two possible B states. Our results demonstrate that the B1 and B2 states correspond to Fe»CO (with carbon atom closer to iron center of heme) and Fe»OC (with oxygen atom closer to Fe), by comparing with the experimental infrared spectrum. QM electrostatic polarization effect on CO brought from the protein and solvent environment is the main driving force, which anchors CO in two distinctive orientations and hinders its rotation. The calculated vibrational frequency shift between the state B1 and B2 is 13.1 cm-1, which is in good agreement with experimental value of 11.5 cm-1. This study also shows that the electric field produced by the solvent plays an important role in assisting protein functions by exerting directional electric field at the active site of the protein. From residue-based electric field decomposition, several residues were found to have most contributions to the total electric field at the CO center, including a few charged residues and three adjacent uncharged polar residues (namely, HIS64, ILE107, and PHE43). This study provides new physical insights on rational design of enzyme with higher electric field at the active site.

Original languageEnglish (US)
Pages (from-to)705-716
Number of pages12
JournalChinese Journal of Chemical Physics
Volume30
Issue number6
DOIs
StatePublished - Dec 27 2017

Fingerprint

myoglobin
Molecular mechanics
Myoglobin
Quantum theory
Carbon Monoxide
Heme
carbon monoxide
Molecular dynamics
quantum mechanics
Electric fields
molecular dynamics
electric fields
Computer simulation
proteins
simulation
Atoms
Proteins
human body
Vibrational spectra
diatomic molecules

Keywords

  • Electric field
  • Electrostatic polarization effect
  • QM/MM simulation
  • Stark shift

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry

Cite this

Ab initio Quantum Mechanics/Molecular Mechanics Molecular Dynamics Simulation of CO in the Heme Distal Pocket of Myoglobin. / Wang, Xian Wei; Zhang, John; He, Xiao.

In: Chinese Journal of Chemical Physics, Vol. 30, No. 6, 27.12.2017, p. 705-716.

Research output: Contribution to journalArticle

@article{0e25daff24c348a0a401df396ba878d7,
title = "Ab initio Quantum Mechanics/Molecular Mechanics Molecular Dynamics Simulation of CO in the Heme Distal Pocket of Myoglobin",
abstract = "Myoglobin has important biological functions in storing and transporting small diatomic molecules in human body. Two possible orientations of carbon monoxide (CO) in the heme distal pocket (named as B1 and B2 states) of myoglobin have been experimentally indicated. In this study, ab initio quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulation of CO in myoglobin was carried out to investigate the two possible B states. Our results demonstrate that the B1 and B2 states correspond to Fe»CO (with carbon atom closer to iron center of heme) and Fe»OC (with oxygen atom closer to Fe), by comparing with the experimental infrared spectrum. QM electrostatic polarization effect on CO brought from the protein and solvent environment is the main driving force, which anchors CO in two distinctive orientations and hinders its rotation. The calculated vibrational frequency shift between the state B1 and B2 is 13.1 cm-1, which is in good agreement with experimental value of 11.5 cm-1. This study also shows that the electric field produced by the solvent plays an important role in assisting protein functions by exerting directional electric field at the active site of the protein. From residue-based electric field decomposition, several residues were found to have most contributions to the total electric field at the CO center, including a few charged residues and three adjacent uncharged polar residues (namely, HIS64, ILE107, and PHE43). This study provides new physical insights on rational design of enzyme with higher electric field at the active site.",
keywords = "Electric field, Electrostatic polarization effect, QM/MM simulation, Stark shift",
author = "Wang, {Xian Wei} and John Zhang and Xiao He",
year = "2017",
month = "12",
day = "27",
doi = "10.1063/1674-0068/30/cjcp1709169",
language = "English (US)",
volume = "30",
pages = "705--716",
journal = "Chinese Journal of Chemical Physics",
issn = "1674-0068",
publisher = "China University of Science and Technology",
number = "6",

}

TY - JOUR

T1 - Ab initio Quantum Mechanics/Molecular Mechanics Molecular Dynamics Simulation of CO in the Heme Distal Pocket of Myoglobin

AU - Wang, Xian Wei

AU - Zhang, John

AU - He, Xiao

PY - 2017/12/27

Y1 - 2017/12/27

N2 - Myoglobin has important biological functions in storing and transporting small diatomic molecules in human body. Two possible orientations of carbon monoxide (CO) in the heme distal pocket (named as B1 and B2 states) of myoglobin have been experimentally indicated. In this study, ab initio quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulation of CO in myoglobin was carried out to investigate the two possible B states. Our results demonstrate that the B1 and B2 states correspond to Fe»CO (with carbon atom closer to iron center of heme) and Fe»OC (with oxygen atom closer to Fe), by comparing with the experimental infrared spectrum. QM electrostatic polarization effect on CO brought from the protein and solvent environment is the main driving force, which anchors CO in two distinctive orientations and hinders its rotation. The calculated vibrational frequency shift between the state B1 and B2 is 13.1 cm-1, which is in good agreement with experimental value of 11.5 cm-1. This study also shows that the electric field produced by the solvent plays an important role in assisting protein functions by exerting directional electric field at the active site of the protein. From residue-based electric field decomposition, several residues were found to have most contributions to the total electric field at the CO center, including a few charged residues and three adjacent uncharged polar residues (namely, HIS64, ILE107, and PHE43). This study provides new physical insights on rational design of enzyme with higher electric field at the active site.

AB - Myoglobin has important biological functions in storing and transporting small diatomic molecules in human body. Two possible orientations of carbon monoxide (CO) in the heme distal pocket (named as B1 and B2 states) of myoglobin have been experimentally indicated. In this study, ab initio quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulation of CO in myoglobin was carried out to investigate the two possible B states. Our results demonstrate that the B1 and B2 states correspond to Fe»CO (with carbon atom closer to iron center of heme) and Fe»OC (with oxygen atom closer to Fe), by comparing with the experimental infrared spectrum. QM electrostatic polarization effect on CO brought from the protein and solvent environment is the main driving force, which anchors CO in two distinctive orientations and hinders its rotation. The calculated vibrational frequency shift between the state B1 and B2 is 13.1 cm-1, which is in good agreement with experimental value of 11.5 cm-1. This study also shows that the electric field produced by the solvent plays an important role in assisting protein functions by exerting directional electric field at the active site of the protein. From residue-based electric field decomposition, several residues were found to have most contributions to the total electric field at the CO center, including a few charged residues and three adjacent uncharged polar residues (namely, HIS64, ILE107, and PHE43). This study provides new physical insights on rational design of enzyme with higher electric field at the active site.

KW - Electric field

KW - Electrostatic polarization effect

KW - QM/MM simulation

KW - Stark shift

UR - http://www.scopus.com/inward/record.url?scp=85041194060&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041194060&partnerID=8YFLogxK

U2 - 10.1063/1674-0068/30/cjcp1709169

DO - 10.1063/1674-0068/30/cjcp1709169

M3 - Article

AN - SCOPUS:85041194060

VL - 30

SP - 705

EP - 716

JO - Chinese Journal of Chemical Physics

JF - Chinese Journal of Chemical Physics

SN - 1674-0068

IS - 6

ER -