QM/MM studies of structural and energetic properties of the far-red fluorescent protein HcRed

Sun, Qiao, Doerr, Markus, Zhen Li,, Smith, Sean C. and Thiel, Walter (2010) QM/MM studies of structural and energetic properties of the far-red fluorescent protein HcRed. Physical Chemistry Chemical Physics, 12 10: 2450-2458. doi:10.1039/b918523b

Author Sun, Qiao
Doerr, Markus
Zhen Li,
Smith, Sean C.
Thiel, Walter
Title QM/MM studies of structural and energetic properties of the far-red fluorescent protein HcRed
Journal name Physical Chemistry Chemical Physics   Check publisher's open access policy
ISSN 1463-9076
Publication date 2010-03-14
Sub-type Article (original research)
DOI 10.1039/b918523b
Open Access Status Not Open Access
Volume 12
Issue 10
Start page 2450
End page 2458
Total pages 9
Place of publication Cambridge, United Kingdom
Publisher Royal Society of Chemistry
Language eng
Formatted abstract
The far-red fluorescent protein HcRed was investigated using molecular dynamics (MD) and combined quantum mechanics/molecular mechanics (QM/MM) calculations. Three models of HcRed (anionic chromophore) were considered, differing in the protonation states of nearby Glu residues (A: Glu214 and Glu146 both protonated; B: Glu214 protonated and Glu146 deprotonated; C: Glu214 and Glu146 both deprotonated). SCC-DFTB/MM MD simulations of model B yield good agreement with the available crystallographic data at ambient pH. Bond lengths in the QM region are well reproduced, with a root mean square (rms) deviation between experimental and average MD data of 0.079 Å; the chromophore is almost co-planar, which is consistent with experimental observation; and the five hydrogen bonds involving the chromophore are conserved. QM/MM geometry optimizations were performed on representative snapshot structures from the MD simulations for each model. They confirm the structural features observed in the MD simulations. According to the DFT(B3LYP)/MM results, the cis-conformation of the chromophore is more stable than the trans-form by 9.1–12.9 kcal mol-1 in model B, and by 12.4–19.9 kcal mol-1 in model C, consistent with the experimental preference for the cis-isomer. However, in model A when both Glu214 and Glu146 are protonated, the stability is inverted with the trans-form being favored. The different protonation states of the titratable active-site residues Glu214 and Glu146 thus critically influence the manner in which the relative stability and degree of planarity of the cis- and trans-conformers vary with pH. Coupled with the known correlation of chromophore conformation with fluorescence efficiency, this work provides a detailed structural basis for the observed phenomenon that red fluorescent proteins such as HcRed, mKate and Rtms5 show bright fluorescence at high pH.
© Royal Society of Chemistry 2011

Keyword Electronic structure calculations
Proton chain transfer
Gaussian basis sets
Crystal structure
Entacmaea quadricolor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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Created: Sun, 14 Mar 2010, 10:00:59 EST