Title page for ETD etd-11242003-225834

Type of Document

Thesis

Author

Xu, Darui

Author's Email Address

dxu@sb.fsu.edu

URN

etd-11242003-225834

Title

Computational Analysis of the U2 Snrna-Intron Duplex

Degree

Master of Science

Department

Chemistry and Biochemistry, Department of

Advisory Committee

Advisor Name	Title
Nancy L. Greenbaum	Committee Chair
Hong Li	Committee Member
Igor Alabugin	Committee Member

Keywords

U2 snRNA
Splicing
Solvation Free Energy
Electrostatics

Date of Defense

2003-11-21

Availability

unrestricted

Abstract

Pairing of a consensus sequence of the precursor (pre)-mRNA intron with a short region
of the U2 small nuclear (sn)RNA during assembly of the eukaryotic spliceosome results in
formation of a complementary helix of seven base pairs with a single unpaired adenosine,
whose 2' OH initiates the nucleophilic attack at the pre-mRNA 5' splice site during the
first step of splicing. The structure of the spliceosomal branch site solved by Newby and
Greenbaum showed that a highly conserved pseudouridine residue in U2 snRNA
induces a dramatically altered structure compared with that of its unmodified counterpart.
In this study, both modified and unmodified U2 snRNA-intron duplexes were analyzed
using computer simulations including preliminary molecular dynamics (MD) simulations,
electrostatic potential, surface area, and solvation free energy calculations. The preliminary
MD simulations produce stable trajectories of the RNA duplexes in solution. The surface
electrostatic potentials were calculated using finite difference Poisson-Boltzmann algorithm
and a hybrid boundary element and finite difference Poisson-Boltzmann approach. Results
show a region of exceptionally negative potential near the 2' OH of the branch site adenosine.
The two RNA duplexes have similar solvent accessible surface areas, whereas the surface
accessible area of the 2' OH of the branch site adenosine of the modified RNA duplex is
considerably smaller than that of the unmodified RNA duplex. The solvation free energy
calculation indicates that the unmodified RNA duplex is favored over the modified RNA
duplex.

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