Single-Walled Carbon Nanotubes Modulate the B- to A-DNA Transition

Abstract

We study the conformational equilibrium between B-to-A forms of ds-DNA adsorbed onto a single-walled carbon nanotube (SWNT) using free energy profile calculations based on all-atom molecular dynamics simulations. The potential of mean force (PMF) of the B-to-A transition of ds-DNA in the presence of an uncharged (10,0) carbon nanotube for two dodecamers with poly-AT or poly-GC sequences is calculated as a function of a root-mean-square-distance (ΔRMSD) difference metric for the B-to-A transition. The calculations reveal that in the presence of a SWNT DNA favors B-form DNA significantly in both poly-GC and poly-AT sequences. Furthermore, the poly-AT DNA:SWNT complex shows a higher energy penalty for adopting an A-like conformation than poly-GC DNA:SWNT by several kcal/mol. The presence of a SWNT on either poly-AT or poly-GC DNA affects the PMF of the transition such that the B form is favored by as much as 10 kcal/mol. In agreement with published data, we find a potential energy minimum between A and B-form DNA at ΔRMSD ≈ -1.5 Å and that the presence of the SWNT moves this minimum by as much as ΔRMSD = 3 Å.

Figure 1

Ideal B- and A-form DNA shown from the top and side, with the outline of the SWNT position during simulations. Note the widening of the interhelical distance and major groove upon converting from B to A form. Double arrows indicate interconversion in a smooth continuous fashion as a response to environmental changes.

Figure 2

Absorbed SWNT on ds-DNA shown from side and front view, in the A and B form. The DNA binds the SWNT in the major groove; conformation used from calculations in ref (7).

Figure 3

Potential of mean force curves generated for poly-GC DNA dodecamer with or without the presence of SWNT fitted into the major groove, plotted against the B-to-A transition gauged via ΔRMSD = RMSD_B – RMSD_A. A negative ΔRMSD represents large B character and little A character, whereas a positive ΔRMSD represents large A character and little B character. The free energy of binding to the SWNT is not included. The well in the bound state near B-like structures is more favored; i.e., along the same curve, B-like forms are favored, as in the case of free DNA.

Figure 4

Potential of mean force curves generated for poly-TA DNA dodecamer with or without the presence of SWNT fitted into the major groove, plotted against the B-to-A transition. Systems with nanotubes present generated force profiles similar to those without SWNT but favor the B form by as much as 10 kcal/mol, with the poly-AT sequence being affected the most.

Figure 5

Averages of RMSD with respect to A and B structures for each window plotted against the position of the ΔRMSD constraint (b) with SWNT present and (a) with no SWNT present. A negative ΔRMSD represents large B character and little A character, whereas a positive ΔRMSD represents large A character and little B character. (a) Shows a smooth transition to A form without SWNT present, whereas (b) shows the difficulty that DNA has in adopting the A form despite the constraint being applied.

Figure 6

Average values of RMSD_A and RMSD_B for each window plotted against a contour plot of the hyperbolic constraint used for umbrella windows. The distance from each data point to the point (−3,0) represents RMSD_A, and RMSD_B is represented by the distance to point (3,0). Several examples of the constraint windows are shown, representing 5 of the 100 windows used to bias sampling along the reaction coordinate ΔRMSD, which is plotted along the abscisa. Each of the hyperbolas plotted here represents the geometric locus of a constant difference between RMSDs relative to ideal A and B forms (which are the two foci of the hyperbolas), with the difference between A and B forms representing the distance between the foci (6 Å).