Prediction of solution properties and dynamics of RNAs by means of Brownian dynamics simulation of coarse-grained models: Ribosomal 5S RNA and phenylalanine transfer RNA

BMC Biophysics

Aarón Ayllón Benítez¹  José Ginés Hernández Cifre¹  Francisco Guillermo Díaz Baños¹  José García de la Torre¹ 

[1] Departamento de Química Física, Universidad de Murcia, Murcia 30100, Spain

关键词: Internal dynamics;    Diffusion coefficients;    Ribosomal RNA;    Transfer RNA;    Hydrodynamics;    Coarse-grained model;    Brownian dynamics;   

Others  :  1234683
DOI  :  10.1186/s13628-015-0025-7

 received in 2015-04-22, accepted in 2015-11-18,  发布年份 2015

【 摘 要 】

Background

The possibility of validating biological macromolecules with locally disordered domains like RNA against solution properties is helpful to understand their function. In this work, we present a computational scheme for predicting global properties and mimicking the internal dynamics of RNA molecules in solution. A simple coarse-grained model with one bead per nucleotide and two types of intra-molecular interactions (elastic interactions and excluded volume interactions) is used to represent the RNA chain. The elastic interactions are modeled by a set of Hooke springs that form a minimalist elastic network. The Brownian dynamics technique is employed to simulate the time evolution of the RNA conformations.

Results

That scheme is applied to the 5S ribosomal RNA of E. Coli and the yeast phenylalanine transfer RNA. From the Brownian trajectory, several solution properties (radius of gyration, translational diffusion coefficient, and a rotational relaxation time) are calculated. For the case of yeast phenylalanine transfer RNA, the time evolution and the probability distribution of the inter-arm angle is also computed.

Conclusions

The general good agreement between our results and some experimental data indicates that the model is able to capture the tertiary structure of RNA in solution. Our simulation results also compare quite well with other numerical data. An advantage of the scheme described here is the possibility of visualizing the real time macromolecular dynamics.

【 授权许可】

   
2015 Benítez et al.

【 参考文献 】

• [1]Bloomfield VA, Crothers DM, Tinoco I. Nucleic Acids. Structures, Properties and Functions. University Science Books, Sausalito California; 2000.
• [2]Noller HF. Structure of ribosomal RNA. Ann Rev Biochem. 1984; 53:119-62.
• [3]Hyeon C, Dima RI, Thirumalai D. Size, shape and flexibility of RNA structures. J Chem Phys. 2006; 125:194905.
• [4]Kim SH, Suddath FL, Quigley GJ, McPherson A, Sussman JL, Wang AHJ et al.. Three-dimensional tertiary structure of yeast phenylalanine transfer RNA. Science. 1974; 185:435-40.
• [5]Hagerman P. Flexibility of RNA. Ann Rev Biophys Biomol Str. 1997; 26:139-56.
• [6]Wang CC, Ford Jr. NC, Fournier MJ. Laser light-scattering analysis of the dimerization of transfer ribonucleic acids with complementary anticodons. Biopolymers. 1981; 20:155-68.
• [7]Patkowski A, Jen S, Chu B. Intensity-fluctuation spectroscopy and tRNA conformation. II. Changes of size and shape of tRNA in the melting process. Biopolymers. 1978; 17:2643-62.
• [8]Porschke D, Antosiewicz J. Permanent dipole moment of tRNA’s and variation of their structure in solution. Biophys J. 1990; 58:403-11.
• [9]Müller JJ, Damaschun G, Wilhelm P, Welfle H, Pilz I. Comparison of the structures of the native form of rat liver 5S rRNA and yeast tRNA: small-angle and wide-angle scattering. Int J Biol Macromol. 1982; 4:289-96.
• [10]Friederich MW, Vacano E, Hagerman PJ. Global flexibility of tertiary structure in RNA: yeast tRNA as a model system. Proc Natl Acad Sci U S A. 1998; 95:3572-7.
• [11]Dynamics of Proteins and Nucleic Acids. Cambridge University Press, Cambridge; 1987.
• [12]Harvey SC, McCammon JA. Intramolecular flexibility in phenylalanine transfer RNA. Nature. 1981; 294:286-7.
• [13]Harvey SC, Prabhakaran M, Mao B, McCammon JA. Phenylalanine transfer RNA: molecular dynamics simulation. Science. 1984; 223:1189-91.
• [14]Tung C-S, Harvey SC, McCammon JA. Large-amplitude bending motions in phenylalanine transfer RNA. Biopolymers. 1984; 23:2173-93.
• [15]Harvey SC, Prabhakaran M, McCammon JA. Molecular-dynamics simulation of phenylalanine transfer RNA. I. Methods and general results. Biopolymers. 1985; 24:1169-88.
• [16]Alexander RW, Eargle J, Luthey-Schulten Z. Experimental and computational determination of tRNA dynamics. FEBS Lett. 2010; 584:376-86.
• [17]Agirrezabala X, Valle M. Structural insights into tRNA dynamics on the ribosome. Int J Mol Sci. 2015; 16:9866-95.
• [18]Fox JW, Wong K-P. The hydrodynamic shape, conformation, and molecular model of Escherichia coli ribosomal 5 S RNA. J Biol Chem. 1979; 254:10139-44.
• [19]Barciszewska MZ, Erdmann VA, Barciszewski J. Ribosomal 5S RNA: tertiary structure and interactions with proteins. Biol Rev. 1996; 71:1-25.
• [20]Skibinska L, Banachowicz E, Gapiński J, Patkowski A, Barciszewski J. Structural similarity of E. coli 5S rRNA in solution and within the ribosome. Biopolymers. 2004; 73:316-25.
• [21]Takada S. Coarse-grained molecular simulations of large biomolecules. Current Opinion in Structural Biology. 2012; 22:130-7.
• [22]García de la Torre J, Navarro S, López Martínez MC, Díaz FG, López Cascales JJ. HYDRO: a computer software for the prediction of hydrodynamic properties of macromolecules. Biophys J. 1994; 67:530-31.
• [23]Carrasco B, García de la Torre J. Hydrodynamic properties of rigid particles. Comparison of different modelling and computational procedures. Biophys J. 1999; 76:3044-57.
• [24]García de la Torre J, Huertas ML, Carrasco B. Calculation of hydrodynamic properties of globular proteins from their atomic-level structures. Biophys J. 2000; 78:719-30.
• [25]García de la Torre J, Pérez Sánchez HE, Ortega A, Hernández Cifre JG, Fernandes MX, Díaz Baños FG et al.. Calculation of the solution properties of flexible macromolecules: methods and applications. Eur Biophys J. 2003; 32:477-86.
• [26]García de la Torre J, Ortega A, Pérez Sánchez HE, Hernández Cifre JG. MULTIHYDRO and MONTEHYDRO: Conformational search and Monte Carlo calculation of solution properties of rigid and flexible macromolecular models. Biophys Chem. 2005; 116:121-8.
• [27]García de la Torre J, Hernández Cifre JG, Ortega A, Rodrígez Schmidt R, Fernandes MX, Pérez Sánchez HE et al.. SIMUFLEX : Algorithms and tools for simulation of the conformation and dynamics of flexible molecules and nanoparticles in solution. J Chem Theor Comput. 2009; 5:2606-18.
• [28]García de la Torre J, Navarro S, López Martínez MC. Hydrodynamic properties of a double-helical model for DNA. Biophys J. 1994; 66:1573-9.
• [29]Tepper H, Voth GA. A coarse-grained model for double-helix molecules in solution: Spontaneous helix formation and equilibrium properties. J Chem Phys. 2005; 122:124906.
• [30]García de la Torre J, Horta A. Sedimentation coefficient and X-ray scattering of double helical model for DNA. J Phys Chem. 1976; 80:2028-35.
• [31]Huertas ML, Navarro S, López Martínez MC, García de la Torre J. Simulation of the conformation and dynamics of a double-helical model for DNA. Biophys J. 1997; 73:3142-53.
• [32]Tozzini V. Coarse-grained models for proteins. Curr Opin Struct Biol. 2005; 15:144-50.
• [33]Xia Z, Gradner DP, Gutell RR, Ren P. Coarse-grained model for simulation of RNA three-dimensional structures. J Phys Chem B. 2010; 114:13497-506.
• [34]Hyeon C, Denesyuk NA, Thirumali D. Development and applications of coarse grained models for RNA. Isr J Chem. 2014; 54:1358-73.
• [35]Réblová K, Lankas F, Rázga F, Krasovska MV, Koca J, Sponer J. Structure, dynamics, and elasticity of free 16S rRNA helix studied by molecular dynamics simulations. Biopolymers. 2006; 82:504-20.
• [36]McDowell SE, Spacková N, Sponer J, Sponer NG. Molecular dynamics simulations of RNA: An in silico single molecule approach. Biopolymers. 2006; 85:169-84.
• [37]Badu SR, Melnik R, Paliy M, Prabhakar S, Sebetci A, Shapiro BA. Modeling of RNA nanotubes using molecular dynamics simulation. Eur Biophys J. 2014; 43:555-64.
• [38]Tanaka Y, Fujii S, Hiroaki H, Sakata T, Tanaka T, Uesugi S et al.. A’-form RNA double helix in the single crystal structure of r(UGAGCUUCGGCUC). Nucleic Acids Res. 1999; 27:949-55.
• [39]Rey A, Freire JJ, García de la Torre J. Monte Carlo calculations for linear and star polymers. 3. Dimensions and hydrodynamic properties in good solvents. Macromolecules. 1987; 20:342-6.
• [40]Ermak DL, McCammon JA. Brownian dynamics with hydrodynamic interactions. J Chem Phys. 1978; 69:1352-60.
• [41]Rotne J, Prager S. Variational treatment of hydrodynamic interaction on polymers. J Chem Phys. 1969; 50:4831-7.
• [42]Rossky PJ, Doll JD, Friedman HL. Brownian dynamics as a smart Monte Carlo method. J Chem Phys. 1978; 69:4628-33.
• [43]Zimm BH. Chain molecule hydrodynamics by the Monte-Carlo method and the validity of the Kirkwood-Riseman approximation. Macromolecules. 1980; 13:592-602.
• [44]Fixman M. Variational bounds for polymer transport coefficients. J Chem Phys. 1983; 78:1588-93.
• [45]Shi H, Moore PB. The crystal structure of yeast phenylalanine tRNA at 1.93 Ȧ resolution: A classic structure revisited. RNA. 2000; 6:1091-105.
• [46]Antosiewicz J, Porschke D. An unusual electrooptical effect observed for DNA fragments and its apparent relation to a permanent electric moment associated with bent DNA. Biophys Chem. 1989; 33:19-30.
• [47]Fernandes MX, Ortega A, López Martínez MC, García de la Torre J. Calculation of hydrodynamic properties of small nucleic acids from their atomic structures. Nucleic Acids Res. 2002; 30:1782-8.
• [48]Müller JJ, Zalkova TN, Ziwer D, Misselwitz R, Gast K, Serdyuk IN et al.. Comparison of the structure of ribosomal 5S RNA from E. coli and from rat liver using x-ray scattering and dynamic light scattering. Eur Biophys J. 1986; 13:301-7.
• [49]Brunel C, Romby P, Westhof E, Ehresmann C, Ehresmann J. Three-dimensional model of escherichia coli ribosomal 5 S RNA as deduced from structure probing in solution and computer modeling. J Mol Biol B. 1991; 221:293-308.
• [50]Erdmann VA, Barciszewski J, Szymansky M, Barciszewska MZ. 5S ribosomal RNA database. Nucleic Acids Res. 2002; 30:176-8.
• [51]Funari SS, Rapp G, Perbandt M, Dierks K, Vallazza M, Betzel C et al.. Structure of free thermus flavus 5S rRNA at 1.3 nm resolution from synchrotron solution scattering. J Biol Chem. 2000; 275:31283-8.
• [52]Amorós D, Ortega A, García de la Torre J. Prediction of hydrodynamic and other solution properties of partially disordered proteins with a simple, coarse-grained model. J Chem Theory Comput. 2013; 9:1678-85.