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Workshops

Dynamics of Protein-Nucleic Acid Interactions: Integrating Simulations with Experiments

September 14, 2011 to September 16, 2011
Location : CECAM-ETHZ, Zurich, Switzerland

Organisers

  • Joanna Trylska (University of Warsaw, Poland)
  • Michael Feig (Michigan State University, East Lansing, USA)
  • Richard Lavery (CNRS - Institute of Biology and Chemistry of Proteins (IBCP), Lyon, France)
  • Martin Zacharias (Technical University of Munich, Germany)
  • Kathleen Hall (Washington University, St. Louis, USA)

Supports

   CECAM



Foundation for Polish Science

Description

Protein-nucleic acid interactions play a central role in fundamental biological processes, especially those related to replication, transcription, and translation. Structural information about many of the involved macromolecular complexes has become available during the last decade, but a full mechanistic understanding that includes key dynamic features is still lacking. In tandem with experimental efforts computer simulations are well-suited to address these questions. Spurred by new structural data and technological advances, an increasing number of simulation studies have recently begun to appear in the literature. While simulations of protein-nucleic acid interactions are frequently discussed from a methodological perspective, this workshop will focus on such themes as protein-nucleic acid binding, sequence-specific recognition, and translocation of proteins along nucleic acids. It also aims at exploring new routes towards combining experimental and simulation approaches to better understand protein-nucleic acid recognition. Such a broader perspective towards a more fundamental understanding of protein-nucleic acid interactions is both timely and critical for guiding future studies in this area.

Crystal structures of large protein-nucleic acid complexes such as the nucleosome [1], RNA polymerase [2] or the ribosome [3] have made it clear that protein-DNA and protein-RNA interactions are of crucial importance to the functioning of biological machines. Understanding these complexes in detail is of great interest because the knowledge of the interactions between proteins and nucleic acids allows for the development of therapeutic approaches interfering with, e. g., viral life cycle or bacterial translation. There have been an increasing number of studies of protein-nucleic acid complexes that address the dynamics of protein-nucleic acid interactions both computationally (reviewed in [4,5]) and experimentally (e.g. recent work on ribosomal dynamics [6]). However, the overall understanding of interactions between proteins and nucleic acids still remains elusive despite much progress over recent years. In order to advance the field further, it is increasingly critical to bring experimental and computational researches together to share information describing the timescales and amplitudes of the dynamics of both nucleic acid and protein, and to devise ways to modulate the dynamics to address their biological significance. Since experimental methods are limited in their ability to investigate molecular motions at the all-atom level, simulations are especially important to understand how dynamics modulate allostery, conformational capture, induced fit, and the role of water and ions at the interface of protein:nucleic acid complexes.

References

[1] K. Luger et al., Crystal structure of the nucleosome core particle at 2.8Å resolution, Nature, 389:251, 1997
[2] P. Cramer et al., Structural basis of transcription: RNA polymerase II at 2.8Å resolution, Science, 292:1863, 2001
[3] A. Liljas – “Structural Aspects of Protein Synthesis”, World Scientific Publishing Co. Pte. Ltd., 2004
[4] A. D. MacKerell Jr. and L. Nilsson, Molecular dynamics simulations of nucleic acid-protein complexes, Curr. Opin. Str. Biol., 18:194, 2008
[5] S. E. McDowell et al., Molecular dynamics simulations of RNA: An in silico single molecule approach, Biopolymers, 85:169, 2006
[6] N. Fischer et al., Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy. Nature, 466:329, 2010