Molecular recognition of RNA: challenges for modelling interactions and plasticity

• Published in: Journal of molecular recognition Vol. 23; no. 2; pp. 220 - 231
• Main Authors: Fulle, Simone, Gohlke, Holger
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2010
• Subjects: A-site; continuum solvent; docking; Drug Design; elastic network model; Ligands; MM/PBSA; Models, Molecular; Molecular Dynamics Simulation; molecular dynamics simulations; Nucleic Acid Conformation; Protein Binding; Protein Conformation; Proteins - chemistry; Proteins - metabolism; ribosome; Ribosome Subunits, Small, Bacterial - chemistry; Ribosome Subunits, Small, Bacterial - metabolism; RNA - chemistry; RNA - metabolism; Thermodynamics; Water - chemistry
• ISSN: 0952-3499; 1099-1352; 1099-1352
• DOI: 10.1002/jmr.1000

There is growing interest in molecular recognition processes of RNA because of RNA's widespread involvement in biological processes. Computational approaches are increasingly used for analysing and predicting binding to RNA, fuelled by encouraging progress in developing simulation, free energy and docking methods for nucleic acids. These developments take into account challenges regarding the energetics of RNA–ligand binding, RNA plasticity, and the presence of water molecules and ions in the binding interface. Accordingly, we will detail advances in force field and scoring function development for molecular dynamics (MD) simulations, free energy computations and docking calculations of nucleic acid complexes. Furthermore, we present methods that can detect moving parts within RNA structures based on graph‐theoretical approaches or normal mode analysis (NMA). As an example of the successful use of these developments, we will discuss recent structure‐based drug design approaches that focus on the bacterial ribosomal A‐site RNA as a drug target. Copyright © 2009 John Wiley & Sons, Ltd.