The conformation of DNA plays an important role in its chemical and biological function as well as for its potential applications in nanotechnology¹. Different conformations of DNA exhibit distinct values for the conductance². Such a distinct conductance can also be used to detect the conformation. DNA mainly adopts A and B conformations at lower and higher hydration levels, respectively^1,2. Experimental and theoretical studies suggest that A to B transformation is smooth and continuous¹, whereas B to A transition is sequence specific, cooperative, and reversible^3,4. To the best of our knowledge, there is no experimental method that can precisely evaluate the electronic structure of DNA during its conformation transition. A recent theoretical study discusses the change in electronic properties during the transformation¹. A recent work found an unexpected result that A-DNA conducts better than B-DNA. To provide insight into the time evolution of the electronic properties during change in conformation, we present a computational investigation of the electrical conductance of 3’-CCCGCGCCC-5’ DNA during various time step of the MD trajectory as the molecule undergoes A to B transition.

The initial structure of A-DNA is built using nucleic acid builder (NAB) in AMBER15. For DNA, the parmbsc1 force field is used and SPC/E force field is used for water and ions. The negative charge on DNA backbone is neutralized with sodium (Na) ions. Additionally, Na⁺ and Cl^- ions are added to achieve 150mM salt concentration. For A to B DNA transformation, A-DNA is placed in water. Further minimization and equilibration is performed according to ABC Minimization⁵. 50 ns molecular dynamics (MD) trajectory is generated with particle mesh Ewald (PME) algorithm and periodic boundary condition (PBC) under constant pressure (isobaric-isothermal ensemble). The transformed B-DNA at the end of 50ns simulation is then placed in 85%ethanol+15%water with 150mM of salt concentration. Packmol is used to model the 85%ethanol+15%water solvent. The temperature is increased to 325K and the simulation is continued for another 48ns. The snapshots during A to B transformations (at 1ps, 50 ps, 100ps, 125ps, 150ps, 200ps and 50000ps, respectively) are considered for electronic structure calculations, where the DNA encounters major structural changes (also done for B to A transformation). Density Functional Theory (DFT) calculations are performed on these structures using GAUSSIAN 09, with the B3LYP functional and 6-31G(d,p) basis set. The electrical conductance of DNA is determined using Landauer formalism with Non-equilibrium Green's function approach².

Figure 1 (a) shows the sugar pucker in the range of 0^o-36^o (representing A-DNA) in the initial phase of simulation that increases step by step to 140^o-180^o (representing B-DNA) and remains in that range till 50ns. We also find that the rise per base pairs increases from ~2.6Å to ~3.4 Å and twist increases from 30-34 Å to 35-38 Å, which confirm the transformation. We could reverse this transformation when the B-DNA is placed in 85%ethanol+15%water at 325K (results not presented here). A-DNA at 1ps has HOMO at -5.04eV and LUMO at -1.04eV. During the transformation, mean value of HOMO energy is -5.06eV and that of LUMO is -1.21eV, indicating significant change in the LUMO energy (~20%). We next look at the charge transport during the transformation, i.e. for the frames at 1 ps, 50 ps, 100 ps, 125 ps, 150ps, 200ps and 50000ps. Overall conductance is seen to decrease (increase) with the A(B) to B(A) transformation (Figure 1 (b) for A to B transformation). It is to be noted that this is the same DNA sequence investigated experimentally² for which the A-conformation exhibits higher conductance than B-conformation. Our simulations clearly verify these experimental findings and provide further information on the evolution of conductance with time. The fluctuations in between could be related to the spatial configurations of counterions, which can alter the conductance of DNA⁶.

References

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2 J.M. Artés, Y. Li, J. Qi, M.P. Anantram, and J. Hihath, Nat. Commun. 6, (2015).

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5 M. Pasi, J.H. Maddocks, D. Beveridge, T.C. Bishop, D.A. Case, I.I.I.T. Cheatham, P.D. Dans, B. Jayaram, F. Lankas, C. Laughton, J. Mitchell, R. Osman, M. Orozco, A. Pérez, D. Petkevičiūtė, N. Spackova, J. Sponer, K. Zakrzewska, and R. Lavery, Nucleic Acids Res. 42, 12272 (2014).

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