Binding Affinity and Conformational Preferences Influence Kinetic Stability of Short Oligonucleotides on Carbon Nanotubes

Abstract

AbstractDNA polymer‐wrapped single‐walled carbon nanotubes (SWNTs) finds a widespread use in a variety of nanotechnology applications. Molecular dynamics (MD) simulations and experiments are used to explore the relationship between structural conformation, binding affinity, and kinetic stability for short single‐stranded oligonucleotides adsorbed on SWNTs. The conformation of 36 oligonucleotide sequences on (9,4) SWNT is computationally screened, where the polymer lengths are selected so the polymers can, to a first approximation, wrap once around the SWNT circumference. The identified conformations can be broadly classified into “rings” and “non‐rings.” Then, 2D conformational free energy landscapes for selected sequences are obtained by temperature replica exchange calculations. Propensity for “ring” conformations are driven primarily by sequence chemistry and the ability of the polymer to form compact structures. However, ring‐formation probability is found to be uncorrelated with free energy of oligonucleotide binding to SWNTs (∆Gbind). Conformational analyses of oligonucleotides, computed free energy of binding of oligonucleotides to SWNTs, and experimentally determined kinetic stability measurements show that ∆Gbind is the primary correlate for kinetic stability. The probability of the sequence to adopt a compact, ring‐like conformation is shown to play a secondary role that still contributes measurably and positively to kinetic stability.