PMID- 19256628
OWN - NLM
STAT- MEDLINE
DCOM- 20090429
LR  - 20211020
IS  - 1089-7690 (Electronic)
IS  - 0021-9606 (Print)
IS  - 0021-9606 (Linking)
VI  - 130
IP  - 8
DP  - 2009 Feb 28
TI  - Dielectric relaxation of cytochrome c oxidase: Comparison of the microscopic and 
      continuum models.
PG  - 085103
LID - 10.1063/1.3060196 [doi]
LID - 085103
AB  - We have studied a charge-insertion process that models the deprotonation of a 
      histidine side chain in the active site of cytochrome c oxidase (CcO) using both 
      the continuum electrostatic calculations and the microscopic simulations. The 
      group of interest is a ligand to Cu(B) center of CcO, which has been previously 
      suggested to play the role of the proton pumping element in the enzyme; the group 
      is located near a large internal water cavity in the protein. Using the 
      nonpolarizable Amber-99 force field in molecular dynamics (MD) simulations, we 
      have calculated the nuclear part of the reaction-field energy of charging of the 
      His group and combined it with the electronic part, which we estimated in terms 
      of the electronic continuum (EC) model, to obtain the total reaction-field energy 
      of charging. The total free energy obtained in this MDEC approach was then 
      compared with that calculated using pure continuum electrostatic model with 
      variable dielectric parameters. The dielectric constant for the "dry" protein and 
      that of the internal water cavity of CcO were determined as those parameters that 
      provide best agreement between the continuum and microscopic MDEC model. The 
      nuclear (MD) polarization alone (without electronic part) of a dry protein was 
      found to correspond to an unphysically low dielectric constant of only about 1.3, 
      whereas the inclusion of electronic polarizability increases the protein 
      dielectric constant to 2.6-2.8. A detailed analysis is presented as to how the 
      protein structure should be selected for the continuum calculations, as well as 
      which probe and atomic radii should be used for cavity definition. The dielectric 
      constant of the internal water cavity was found to be 80 or even higher using 
      "standard" parameters of water probe radius, 1.4 A, and protein atomic radii from 
      the MD force field for cavity description; such high values are ascribed to the 
      fact that the standard procedure produces unphysically small cavities. Using 
      x-ray data for internal water in CcO, we have explored optimization of the 
      parameters and the algorithm of cavity description. For Amber radii, the optimal 
      probe size was found to be 1.25 A; the dielectric of water cavity in this case is 
      in the range of 10-16. The most satisfactory cavity description, however, was 
      achieved with ProtOr atomic radii, while keeping the probe radius to be standard 
      1.4 A. In this case, the value of cavity dielectric constant was found to be in 
      the range of 3-6. The obtained results are discussed in the context of recent 
      calculations and experimental measurements of dielectric properties of proteins.
FAU - Leontyev, I V
AU  - Leontyev IV
AD  - Department of Chemistry, University of California, One Shields Avenue, Davis, 
      California 95616, USA.
FAU - Stuchebrukhov, A A
AU  - Stuchebrukhov AA
LA  - eng
GR  - R01 GM054052/GM/NIGMS NIH HHS/United States
GR  - R29 GM054052/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Chem Phys
JT  - The Journal of chemical physics
JID - 0375360
RN  - 0 (Ligands)
RN  - 059QF0KO0R (Water)
RN  - 4QD397987E (Histidine)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
CIN - J Chem Phys. 130:085102. PMID: 19256627
MH  - Catalytic Domain
MH  - Computer Simulation
MH  - Electron Transport Complex IV/*chemistry
MH  - Histidine/chemistry
MH  - Ligands
MH  - *Models, Chemical
MH  - Static Electricity
MH  - Water/chemistry
PMC - PMC2671215
EDAT- 2009/03/05 09:00
MHDA- 2009/04/30 09:00
PMCR- 2010/02/28
CRDT- 2009/03/05 09:00
PHST- 2009/03/05 09:00 [entrez]
PHST- 2009/03/05 09:00 [pubmed]
PHST- 2009/04/30 09:00 [medline]
PHST- 2010/02/28 00:00 [pmc-release]
AID - 511848JCP [pii]
AID - 10.1063/1.3060196 [doi]
PST - ppublish
SO  - J Chem Phys. 2009 Feb 28;130(8):085103. doi: 10.1063/1.3060196.