Bubble Relaxation Dynamics in Homopolymer DNA Sequences

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Feb 11

PMID 36770707

Authors

Malcolm Hillebrand

George Kalosakas

Alan R Bishop

Charalampos Skokos

Affiliations

Soon will be listed here.

Abstract

Understanding the inherent timescales of large bubbles in DNA is critical to a thorough comprehension of its physicochemical characteristics, as well as their potential role on helix opening and biological function. In this work, we employ the coarse-grained Peyrard-Bishop-Dauxois model of DNA to study relaxation dynamics of large bubbles in homopolymer DNA, using simulations up to the microsecond time scale. By studying energy autocorrelation functions of relatively large bubbles inserted into thermalised DNA molecules, we extract characteristic relaxation times from the equilibration process for both adenine-thymine (AT) and guanine-cytosine (GC) homopolymers. Bubbles of different amplitudes and widths are investigated through extensive statistics and appropriate fittings of their relaxation. Characteristic relaxation times increase with bubble amplitude and width. We show that, within the model, relaxation times are two orders of magnitude longer in GC sequences than in AT sequences. Overall, our results confirm that large bubbles leave a lasting impact on the molecule's dynamics, for times between 0.5-500 ns depending on the homopolymer type and bubble shape, thus clearly affecting long-time evolutions of the molecule.

References

Alexandrov B, Gelev V, Yoo S, Bishop A, Rasmussen K, Usheva A . Toward a detailed description of the thermally induced dynamics of the core promoter. PLoS Comput Biol. 2009; 5(3):e1000313. PMC: 2645506. DOI: 10.1371/journal.pcbi.1000313. View

Wang X, Sun Z . Determination of Base-Flipping Free-Energy Landscapes from Nonequilibrium Stratification. J Chem Inf Model. 2019; 59(6):2980-2994. DOI: 10.1021/acs.jcim.9b00263. View

Kalosakas G . Charge transport in DNA: dependence of diffusion coefficient on temperature and electron-phonon coupling constant. Phys Rev E Stat Nonlin Soft Matter Phys. 2011; 84(5 Pt 1):051905. DOI: 10.1103/PhysRevE.84.051905. View

Hsu C, Fyta M, Lakatos G, Melchionna S, Kaxiras E . Ab initio determination of coarse-grained interactions in double-stranded DNA. J Chem Phys. 2012; 137(10):105102. DOI: 10.1063/1.4748105. View

Sobell H . Actinomycin and DNA transcription. Proc Natl Acad Sci U S A. 1985; 82(16):5328-31. PMC: 390561. DOI: 10.1073/pnas.82.16.5328. View

Freeman G, Hinckley D, Lequieu J, Whitmer J, de Pablo J . Coarse-grained modeling of DNA curvature. J Chem Phys. 2014; 141(16):165103. DOI: 10.1063/1.4897649. View

Galindo-Murillo R, Roe D, Cheatham 3rd T . On the absence of intrahelical DNA dynamics on the μs to ms timescale. Nat Commun. 2014; 5:5152. PMC: 4215645. DOI: 10.1038/ncomms6152. View

Banerjee D, Kumar Pal S . Direct observation of essential DNA dynamics: melting and reformation of the DNA minor groove. J Phys Chem B. 2007; 111(36):10833-8. DOI: 10.1021/jp074697n. View

Alexandrov B, Gelev V, Yoo S, Alexandrov L, Fukuyo Y, Bishop A . DNA dynamics play a role as a basal transcription factor in the positioning and regulation of gene transcription initiation. Nucleic Acids Res. 2009; 38(6):1790-5. PMC: 2847213. DOI: 10.1093/nar/gkp1084. View

10.

Ares S, Kalosakas G . Distribution of bubble lengths in DNA. Nano Lett. 2007; 7(2):307-11. DOI: 10.1021/nl062304a. View

11.

Beece D, Eisenstein L, Frauenfelder H, Good D, Marden M, Reinisch L . Solvent viscosity and protein dynamics. Biochemistry. 1980; 19(23):5147-57. DOI: 10.1021/bi00564a001. View

12.

Choi C, Kalosakas G, Rasmussen K, Hiromura M, Bishop A, Usheva A . DNA dynamically directs its own transcription initiation. Nucleic Acids Res. 2004; 32(4):1584-90. PMC: 390311. DOI: 10.1093/nar/gkh335. View

13.

Peyrard , BISHOP . Statistical mechanics of a nonlinear model for DNA denaturation. Phys Rev Lett. 1989; 62(23):2755-2758. DOI: 10.1103/PhysRevLett.62.2755. View

14.

Dauxois , Peyrard , BISHOP . Dynamics and thermodynamics of a nonlinear model for DNA denaturation. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 1993; 47(1):684-695. DOI: 10.1103/physreve.47.684. View

15.

Hillebrand M, Kalosakas G, Schwellnus A, Skokos C . Heterogeneity and chaos in the Peyrard-Bishop-Dauxois DNA model. Phys Rev E. 2019; 99(2-1):022213. DOI: 10.1103/PhysRevE.99.022213. View

16.

Perez A, Luque F, Orozco M . Dynamics of B-DNA on the microsecond time scale. J Am Chem Soc. 2007; 129(47):14739-45. DOI: 10.1021/ja0753546. View

17.

Tapia-Rojo R, Mazo J, Hernandez J, Peleato M, Fillat M, Falo F . Mesoscopic model and free energy landscape for protein-DNA binding sites: analysis of cyanobacterial promoters. PLoS Comput Biol. 2014; 10(10):e1003835. PMC: 4183373. DOI: 10.1371/journal.pcbi.1003835. View

18.

Kalosakas G, Ares S . Dependence on temperature and guanine-cytosine content of bubble length distributions in DNA. J Chem Phys. 2009; 130(23):235104. DOI: 10.1063/1.3149859. View

19.

Tapia-Rojo R, Mazo J, Falo F . Thermal and mechanical properties of a DNA model with solvation barrier. Phys Rev E Stat Nonlin Soft Matter Phys. 2011; 82(3 Pt 1):031916. DOI: 10.1103/PhysRevE.82.031916. View

20.

Lavery R, Zakrzewska K, Beveridge D, Bishop T, Case D, Cheatham 3rd T . A systematic molecular dynamics study of nearest-neighbor effects on base pair and base pair step conformations and fluctuations in B-DNA. Nucleic Acids Res. 2009; 38(1):299-313. PMC: 2800215. DOI: 10.1093/nar/gkp834. View