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January 2009 - March 2010

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St. Olaf College
Department of Chemistry

PI: Jeff Schwinefus

Urea Preferential Interactions With Nucleic Acids: A Molecular Dynamics Study

In order to gain full comprehension of nucleic acid structure destabilization with cosolutes (amino acids, nucleic acid precursors, simple sugars, and metabolites), molecular dynamics (MD) simulations have been combined with vapor pressure osmometry to elucidate the mode of interaction between urea and nucleic acid nucleobases. Over the past period, these researchers have used MSI resources to simulate adenosine, cytidine, guanosine, thymidine, and uridine nucleotides in urea-free and 1 m urea solutions using Amber 10 MD software. The majority of urea accumulation around nucleobases occurs parallel to the base planes above and below the base, suggesting - interactions between urea and the nucleobase. Preferential interaction coefficients from vapor pressure osmometry scale with nucleobase accessible surface area (ASA), as suggested by MD results. This result is significant for two reasons. First, urea interactions with biopolymers may occur through - interactions as well as interactions with amide or amide-like functional groups; these latter interactions have been identified as the major interaction leading to protein denaturation in aqueous urea solutions. Secondly, this mechanism of interaction explains why urea destabilizes AT- and AU-rich double helices to a greater extent than GC-rich double helices. 

Future work will extend all MD simulations (with or without urea) to 60 ns to identify key functional groups (i.e. nucleobases) with urea preferential interactions and couple these MD results with vapor pressure osmometry studies at St. Olaf College. Additionally, the researchers will determine syn-anti distributions in the mononucleotides. They have found from the MD simulations that the syn conformation in the uridine mononucleotide is accompanied by a sodium ion interacting with O4' on the sugar and an oxygen on the phosphate group. The resarchers will search for similar sodium ion placements in the anti-syn conversion of the other mononucleotides as well to identify any common theme for this transition.

Group Members

Kris Elbein, Undergraduate Student
Elliot Schmidt, Undergraduate Student