title: Computational design of RNA libraries for in vitro selection of aptamers.
abstract: Selection of aptamers that bind a specific ligand usually begins with a random library of RNA sequences, and many aptamers selected from such random pools have a simple stem-loop structure. We present here a computational approach for designing a starting library of RNA sequences with increased formation of complex structural motifs and enhanced affinity to a desired target molecule. Our approach consists of two steps: (1) generation of RNA sequences based on customized patterning of nucleotides with increased probability of forming a base pair and (2) a high-throughput virtual screening of the generated library to select aptamers with binding affinity to a small-molecule target. We developed a set of criteria that allows one to select a sequence with potential binding affinity from a pool of random sequences and designed a protocol for RNA 3D structure prediction. The proposed approach significantly reduces the RNA sequence search space, thus accelerating the experimental screening and selection of high-affinity aptamers.
authors.affiliation: The Henry M. Jackson Foundation, Bethesda, MD, USA.
authors.forename: Yaroslav G
authors.initials: YG
authors.lastname: Chushak
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Martin
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Chávez
authors.forename: Nancy
authors.initials: N
authors.lastname: Kelley-Loughnane
authors.forename: Morley O
authors.initials: MO
authors.lastname: Stone
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry*; D020029:Base Pairing; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*
chemical_list: D052157:Aptamers, Nucleotide; D012313:RNA