Red Fluorescent Protein DsRed: Parametrization of Its Chromophore as an Amino Acid Residue for Computer Modeling in the OPLS-AA Force Field

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D. V. Dmitrienko^1,2, E. P. Vrzheshch^1,3, V. L. Drutsa⁴, and P. V. Vrzheshch^1,5*

¹Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-4218; E-mail: peter@genebee.msu.ru

²Faculty of Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-2776

³Emmanuel Institute of Biochemical Physics, Russian Academy of Sciences, ul. Kosygina 4, 117997 Moscow, Russia; fax: (495) 137-4101; E-mail: ibcp@sky.chph.ras.ru

⁴Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-0338; E-mail: drutsa@genebee.msu.su

⁵International Biotechnological Center, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-5022; E-mail: info@biocentr.msu.ru

^* To whom correspondence should be addressed.

Received May 10, 2006; Revision received June 17, 2006

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Topology of the neutral form of the DsRed fluorescent protein chromophore as a residue of [(4-cis)-2-[(1-cis)-4-amino-4-oxobutanimidoyl]-4-(4-hydroxybenzylidene)-5-oxo-4,5-dihydro-1H-imidazol-1-yl]acetic acid was calculated with OPLS-AA force field. Use of this topology and molecular dynamics simulation allows calculating the parameters of proteins that contain such residue in their polypeptide chains. The chromophore parameters were obtained by ab initio (RHF/6-31G**) quantum chemical calculations applying density functional theory (B3LYP). Using this chromophore, we have calculated the molecular dynamics trajectory of tetrameric fluorescent protein DsRed in solution at 300 K (4 nsec). Correctness of the chromophore parametrization was revealed by comparison of quantitative characteristics of the chromophore structure obtained from the molecular dynamic simulations of DsRed protein with the quantitative characteristics of the chromophore based on the crystallographic X-ray data of fluorescent protein DsRed (PDB ID: 1ZGO, 1G7K, and 1GGX), and also with the quantitative characteristics of the chromophore obtained by quantum chemical calculations. Inclusion of the neutral form of DsRed protein chromophore topology into the OPLS-AA force field yielded the extended force field OPLS-AA/DsRed. This force field can be used for molecular dynamics calculations of proteins containing the DsRed chromophore. The parameter set presented in this study can be applied for similar extension in any other force fields.

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KEY WORDS: red fluorescent protein, DsRed, chromophore, quantum chemical calculations, topology, OPLS-AA, molecular dynamics

DOI: 10.1134/S0006297906100129

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