title: The effects of multiple probes on the hybridization of target DNA on surfaces.
abstract: DNA microarrays have disruptive potential in many fields including genetics and medicine, but the technology has yet to find widespread clinical use due to poor reliability. Microarrays work on the principle of hybridization and can only be as dependable as this process is reliable. As such, a significant amount of theoretical research has been done to understand hybridization on surfaces on the molecular level. Previous simulations of a target strand with a single, surface-tethered probe molecule have yielded valuable insights, but such is an ideal system and little is known about the effects of multiple probes-a situation that more closely approximates the real system. This work uses molecular simulation to determine the specific differences in duplex stability between one, three, six, and nine tethered probes on a surface. The results show that it is more difficult for a single target to hybridize to a probe as the number of probes on the surface increases due to crowding effects; however, once hybridized, the duplex is more stable than when fewer probes are present. The data also indicate that hybridization of a target to a probe on the face of a group of probes is more stable than hybridization to probes at the edge or center locations. Taken as a whole, the results offer new insights into the cause of the poor reproducibility exhibited by microarrays.
authors.affiliation: Department of Chemical Engineering, Brigham Young University, Provo, Utah 84602, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Welling
authors.affiliation: Department of Chemical Engineering, Brigham Young University, Provo, Utah 84602, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Knotts
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000235:genetics; D015342:DNA Probes / Q000737:chemistry*; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D013499:Surface Properties
chemical_list: D015342:DNA Probes; D004247:DNA; D004250:DNA Topoisomerases, Type II