Studies on the solution structure dynamics of RNA/DNA now-a-days becoming crucially important for understanding various phenomena related to gene control reagents such as antisense RNA/DNA, RNAi, non-coding microRNAs and other newer families of functional RNA. A short single-stranded (ss) DNA or RNA molecule can be thought of conformationally not as short strings but rather as sequence dependent folded structure which adopts, with comparable probability, many different conformations in solution that distinguishes it from other biological macromolecules. What are typical conformations of short ssDNA and what factors govern their conformational space? To answer these and similar questions which concern the intimate behavior of ssDNA require the knowledge of accurate molecular conformations.

For this purposes, we have studied a general nature of SSCP phenomenon at the oligodexynucleotide level by gel electrophoresis and molecular dynamics (MD). SSCP is the separation of single-stranded nucleic acids based on subtle differences in sequence (often a single base) which results in a different secondary structure and a measurable difference in mobility during electrophoresis. The valuable qualitative data of electrophoresis could be further explored more in conjunction of introducing the quantitative aide of computational MD simulation: to create a graphical representation of the experimental structure, to generate hypothetical model and to predict new physical properties. We found a general feature of the SSCP phenomenon by studying the simpler molecules of ss-oligodeoxyribonucleotides. A single base substitution or a positional exchange of nucleotide in a highly homologous series of ss-dodecanucleotides led to a change in the mobility-in-gel. MD experiments revealed differences in shape and size between the dynamic structures of these molecules which could affect their mobility-in-gel (see Fig. below). A high correlation between the electrophoretic mobility and the size-related parameters obtained from MD shows the significance of negligibly weak, intra-molecular interactions between adjacent nucleotides of a strand, which can and do contribute to the distribution of dynamic structures in solution representing SSCP phenomenon. The knowledge about solution structure dynamics of ssDNA appear to be beneficial to understand various phenomena to control gene networking. 

References:

• Manish Biyani and Koichi Nishigaki (2005) Single-strand conformation polymorphism at the
      oligodeoxyribonucleotide level: An insight into solution structural dynamics of DNAs by gel
      lectrophoresisand molecular dynamics simulations. J Biochem 138(4), 363-373.
• Manish Biyani and Koichi Nishigaki (2003) Sequence-specific and non-specific mobilities of single-
      stranded oligonucleotides observed by changing the borate buffer concentration. Electrophoresis,
      24(4),628-633.
• Manish Biyani and Koichi Nishigaki. (2003) Prediction from Sequence to Structure at
      oligonucleotides level by MD simulations. In: Proc. of 14th International conference on Genome
      Informatics 2003, Gribskov, M., Kanehisa, M., Miyano, S., Takagi, T. (ed.), Universal academy
      press,Japan, vol.14, p.p.490-491.