RAGPOOLS- RNA-As-Graph-PoolsA Web Server to Assist the.pptVIP

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RAGPOOLS- RNA-As-Graph-PoolsA Web Server to Assist the.ppt

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RAGPOOLS: RNA-As-Graph-PoolsA Web Server to Assist the Design of Structured RNA Pools for In-Vitro Selection Namhee Kim Laboratory of Prof. Tamar Schlick 1.1. In Vitro Selection 1.2.Targeted RNA Pool Design Already an experimental goal J.H. Davis and J.W. Szostak, Proc. Natl. Acad. Sci. 99:11616 (2002) M.W. Lau, K.E. Cadieux, and P.J. Unrau, J. Am. Chem. Soc. 126:15686 (2004) Random pools are biased to simple topologies Complex structures are more active 2. Modeling of Pool Synthesis 3. Algorithm for Structured Pool Design Examples of Structured Pools Acknowledgments Prof. Tamar Schlick Dr. Hin Hark Gan Jin Sup Shin Shereef Elmetwaly All members of the Schlick Lab Mixing Matrix Motivated by Biological Mutations Starting Sequences and Coverage of Sequence Space Motif Distributions GTP Aptamer Pool * NYU/BIOMATH * * The 3rd Annual ROC Meeting – Madison, WI May 28-29, 2007 1. RNA Pool Design for In Vitro Selection 2. Modeling of Pool Synthesis 3. Features of RAGPOOLS 4. Conclusions New York University An experimental approach to screen large (~1015) random- sequence libraries of RNAs for a specific function (e.g., binding property) Numerous aptamers and ribozymes were discovered from in vitro selection D. Wilson and J.W. Szostak, Annu.Rev.Biochem 68:611 (1999) N. Kim, H.H. Gan, and T. Schlick, RNA 13:478 (2007) Proposal Design better pools by mixing base composition to target novel structures J. Gevertz et al., RNA 11:853 (2005) J. Carothers et al., J. Am. Chem. Soc. 126:5130 (2004) By optimizing compositions of A, U, C and G in four containers (Mixing Matrix) and starting sequence, we seek to design pools with target topologies e.g., 40% 20% 10% 30% A 20% 30% 40% 10% U 30% 10% 20% 20% G 10% 40% 30% 40% C instead of 25% 25% 25% 25% A 25% 25% 25% 25% U 25% 25% 25% 25% G 25% 25% 25% 25% C Step 1.