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Minimum sequence requirements for selective RNA‐ligand binding: A molecular mechanics algorithm using molecular dynamics and free‐energy techniques
Author(s) -
Anderson Peter C.,
Mecozzi Sandro
Publication year - 2006
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20459
Subject(s) - molecular dynamics , molecular mechanics , rna , algorithm , sequence (biology) , computer science , parameterized complexity , biological system , chemistry , computational biology , computational chemistry , biology , biochemistry , gene
In vitro evolution techniques allow RNA molecules with unique functions to be developed. However, these techniques do not necessarily identify the simplest RNA structures for performing their functions. Determining the simplest RNA that binds to a particular ligand is currently limited to experimental protocols. Here, we introduce a molecular‐mechanics based algorithm employing molecular dynamics simulations and free‐energy methods to predict the minimum sequence requirements for selective ligand binding to RNA. The algorithm involves iteratively deleting nucleotides from an experimentally determined structure of an RNA‐ligand complex, performing energy minimizations and molecular dynamics on each truncated structure, and assessing which truncations do not prohibit RNA binding to the ligand. The algorithm allows prediction of the effects of sequence modifications on RNA structural stability and ligand‐binding energy. We have implemented the algorithm in the AMBER suite of programs, but it could be implemented in any molecular mechanics force field parameterized for nucleic acids. Test cases are presented to show the utility and accuracy of the methodology. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006