Computer-aided design of aptamers for cytochrome p450

J Struct Biol. 2015 Aug;191(2):112-9. doi: 10.1016/j.jsb.2015.07.003. Epub 2015 Jul 10.

Abstract

Aptamers are short single-stranded DNA or RNA oligonucleotides that can bind to their targets with high affinity and specificity. Usually, they are experimentally selected using the SELEX method. Here, we describe an approach toward the in silico selection of aptamers for proteins. This approach involves three steps: finding a potential binding site, designing the recognition and structural parts of the aptamers and evaluating the experimental affinity. Using this approach, a set of 15-mer aptamers for cytochrome P450 51A1 was designed using docking and molecular dynamics simulation. An experimental evaluation of the synthesized aptamers using SPR biosensor showed that these aptamers interact with cytochrome P450 51A1 with Kd values in the range of 10(-6)-10(-7) M.

Keywords: Aptamer; Bioinformatics; Cytochrome P450 51A1; Molecular docking; Molecular dynamics; Rational design; SELEX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide / chemistry*
  • Binding Sites
  • Cytochrome P-450 Enzyme System / chemistry*
  • Models, Molecular
  • Molecular Docking Simulation / methods
  • Molecular Dynamics Simulation
  • Nucleic Acid Conformation
  • Protein Structure, Tertiary
  • Structure-Activity Relationship

Substances

  • Aptamers, Nucleotide
  • Cytochrome P-450 Enzyme System