Tags

Type your tag names separated by a space and hit enter

QM/MM studies of structural and energetic properties of the far-red fluorescent protein HcRed.
Phys Chem Chem Phys 2010; 12(10):2450-8PC

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 A; 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.

Authors+Show Affiliations

Centre for Computational Molecular Science, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Qld 4072, Brisbane, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20449359

Citation

Sun, Qiao, et al. "QM/MM Studies of Structural and Energetic Properties of the Far-red Fluorescent Protein HcRed." Physical Chemistry Chemical Physics : PCCP, vol. 12, no. 10, 2010, pp. 2450-8.
Sun Q, Doerr M, Li Z, et al. QM/MM studies of structural and energetic properties of the far-red fluorescent protein HcRed. Phys Chem Chem Phys. 2010;12(10):2450-8.
Sun, Q., Doerr, M., Li, Z., Smith, S. C., & Thiel, W. (2010). QM/MM studies of structural and energetic properties of the far-red fluorescent protein HcRed. Physical Chemistry Chemical Physics : PCCP, 12(10), pp. 2450-8. doi:10.1039/b918523b.
Sun Q, et al. QM/MM Studies of Structural and Energetic Properties of the Far-red Fluorescent Protein HcRed. Phys Chem Chem Phys. 2010 Mar 14;12(10):2450-8. PubMed PMID: 20449359.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - QM/MM studies of structural and energetic properties of the far-red fluorescent protein HcRed. AU - Sun,Qiao, AU - Doerr,Markus, AU - Li,Zhen, AU - Smith,Sean C, AU - Thiel,Walter, Y1 - 2010/01/19/ PY - 2010/5/8/entrez PY - 2010/5/8/pubmed PY - 2010/8/6/medline SP - 2450 EP - 8 JF - Physical chemistry chemical physics : PCCP JO - Phys Chem Chem Phys VL - 12 IS - 10 N2 - 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 A; 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. SN - 1463-9084 UR - https://www.unboundmedicine.com/medline/citation/20449359/QM/MM_studies_of_structural_and_energetic_properties_of_the_far_red_fluorescent_protein_HcRed_ L2 - https://doi.org/10.1039/b918523b DB - PRIME DP - Unbound Medicine ER -