Quantum dot–DNA interaction: Computational issues and preliminary insights on use of quantum dots as biosensors

In recent years, quantum dots have generated enormous interest from the life sciences community due to their (largely) untapped potential in biomedical applications; particularly in bio-labeling and sensing. While empirical work already exists on the use of quantum dots as bio-labels, their development as biosensors requires a thorough scientific understanding of their interactions with conjugated biomolecules that together ‘sense’ the molecule of interest. Some recent experiments have claimed a marked variation in the luminescence of cadmium selenide quantum dots conjugated to macromolecules linked to bacteria. The origin of this large shift in luminescence of the quantum dot (and thus by implication, the band gap) appears to be poorly understood. The knowledge of the exact nature of the interaction causing the ‘shift’ may hold the key to designing better biosensors. The objective of the present work is to address the aforementioned interaction and to that end, we have chosen a prototypical model consisting of a capped cadmium selenide quantum dot interacting with a DNA molecule. This problem is inherently multiscale due to the relatively large number of atoms, complex nature of the interactions involved in the quantum dot–DNA system and the disparate length scales present in the problem requiring a combination of methods ranging from approaches that utilize empirical molecular mechanics force fields on one hand and ab initio electronic structure (based on density functional theory) calculations on the other hand. We discuss several modeling issues that arise in the simulations of this complex problem and present some preliminary insights. Our initial results indicate a wavelength shift of roughly 19 nm in the spectrum of a 1.1 nm sized dot upon interaction with a typical DNA molecule. However, upon increase of quantum dot size, the shift decreases and thus suggests a re-examination of singular experimental data available in the literature. Our results, which are performed in vacuum rather than a solvent, may be considered as an upper-bound to the true interaction.