Research Programmes

• Advanced Nanotechnologies and Microtechnologies
  • Functional Properties of Nanostructures
  • Submicron Systems and Nanodevices
  • Experimental Biophotonics
  • Fabrication and Characterisation of Nanostructures
  • Development of Methods for Analysis and Measuring
  • X-ray Micro CT and Nano CT
  • Optoelectronic Characterisation of Nanostructures
  • Micro and Nanotribology
  • Plasma Technologies
  • Synthesis and Analysis of Nanostructures
  • Transport and Magnetic Properties
• Advanced Materials
  • Advanced Ceramic Materials
  • Materials for Sensors and Technological Processes Control Systems
  • Advanced Polymers and Composites
  • Advanced Metallic Materials and Metal Based Composites
  • Structure and Phase Analysis
• Structural Biology
  • Bioinformatics
  • CD Spectroscopy of Nucleic Acids and Proteins
  • CryoEM
  • Glycobiochemistry
  • RNA Quality Control
  • Nanobiotechnology
  • Biomolecular NMR Spectroscopy
  • NMR Spectroscopy II
  • NMR Spectroscopy III
  • Protein/RNA Interactions
  • X-ray Crystallography I
  • X-ray Crystallography II
  • Structure and Dynamics of Nucleic Acids
  • Structure and Interaction of Biomolecules at Surfaces
  • Computational Chemistry
• Genomics and Proteomics of Plant Systems
  • Bioanalytical Instrumentation
  • Plant Cytogenomics
  • Functional Genomics and Proteomics of Plants
  • Hormonal Crosstalk in Plant Development
  • Metabolomics
  • Core Facility – Proteomics
  • Developmental and Cell Biology of Plants
  • Chromatin Molecular Complexes
  • Developmental and Production Biology – Omics Approaches
• Molecular Medicine
  • Medical Genomics
  • Molecular Oncology I – Hematooncology
  • Molecular Oncology II – Solid Cancer
  • Inherited Diseases I – Genetic Research
  • Inherited Diseases II – Transcriptional Regulation
  • Molecular Immunology and Microbiology
  • Molecular Gastroenterology and Hepatology
  • Genome Dynamics
  • Core Facility – Genomics
  • Laboratory of Human Molecular Genetics
• Brain and Mind Research
  • Cellular and Molecular Neurobiology
  • Molecular and Functional Neuroimaging
  • Experimental and Applied Neuropsychopharmacology
  • Psychophysiology
  • Behavioural and Social Neuroscience
  • Applied Neuroscience
• Molecular Veterinary Medicine
  • Molecular Virology
  • Molecular Bacteriology
  • Parasitology
  • Food Safety
  • Orthopaedics and Surgery
  • Animal Imunogenomics
  • Animal Cytogenomics
  • Mammalian Reproduction

Structure and Dynamics of Nucleic Acids

Prof. RNDr. Jiří Šponer, DrSc.
Research Group Leader

THEMATIC RESEARCH FOCUS

RESEARCH AREAS

• Studies of structure, dynamics and molecular interactions of nucleic acids and their complexes with proteins using explicit solvent molecular dynamics simulations; main attention is paid to functional RNAs, such as ribosomal RNAs and catalytic RNAs
• Quantum chemical modelling of processes relevant to the prebiotic synthesis of nucleic acid components
• Structural bioinformatics of RNA (classifi cation of molecular interactions in nucleic acids based on structural and sequence data)
• Testing and refi nement of force fi elds for atomistic simulations of nucleic acids
• Reference quantum-chemical calculations of molecular interactions and conformational substates in nucleic acids

MAIN OBJECTIVES

• Investigation of the role of RNA in development and human diseases.
• Development of new methodologies for investigating the structure, interactions, and dynamics of biomolecules.

CONTENT OF RESEARCH

Computational studies, combining a full range of leading computational methods (explicit solvent molecular dynamics simulations, quantum-chemical calculations, hybrid quantum-classical calculations and bioinformatics), will be used to unravel the key features of the RNA structure and the role of RNA in protein biosynthesis. The work will be initially devoted to ribosome and ribozymes where atomic resolution information is available. The research will be gradually extended to other RNA systems where enough experimental structural data is available.

Modern computational techniques can fill several major gaps in the present knowledge of the RNA function. We will classify RNA building blocks and their molecular interactions, to unravel the link between their physical-chemical properties and evolutionary patterns. We will analyse chemical reactions at the atomistic level of electronic structure description to capture catalytic strategies of ribozymes and to model prebiotic chemical reactions.

Free energy calculations, or molecular dynamics simulations, often critically depend on the adequacy of the molecular mechanical force fields and other methods describing the relation between molecular structures and energies. Therefore, much effort will be devoted to the development and verification of these methods. This will mainly be done in the field of nucleic acids, where the main attention will be paid to noncanonical architectures such as hairpin loops, which are notoriously difficult to describe by the force fields.

KEY RESEARCH EQUIPMENT

PLANNED RESEARCH INFRASTRUCTURE

Technology Units

Structure and dynamics of nucleic acids – computer equipment

CURRENT RESEARCH INFRASTRUCTURE

The laboratory is presently equipped with three computer clusters. The first cluster contains 15 nodes with a total number of 30 CPUs (Intel Xeon 3.0 GHz), the second contains 30 nodes with a total number of 120 primitive (core) CPUs (AMD Opteron 285 and AMD Opteron 2220 DualCore) and the last one contains 43 nodes with a total number of 344 core CPUs (Intel Xeon E5430 QuadCore).

MAIN PROJECTS

• Structural dynamics, molecular interactions and function of key RNA motifs (GA203/09/1476), Czech Science Foundation, 2009-2012, J. Šponer, Institute of Biophysics AS CR.
• Structure and dynamics of DNA. Advanced computational studies (GAP208/11/1822), Czech Science Foundation, 2011-2015, J. Šponer, Institute of Biophysics AS CR.
• Structure, dynamics, and reaction mechanism of catalytic RNA (IAA400040802), Academy of Sciences of the Czech Republic, 2008-2011, J. Šponer, Institute of Biophysics AS CR, L. Rulišek, Institute of Organic Chemistry and Biochemistry AS CR, M. Otyepka, Palacky University Olomouc.
• Biomolecular Center (LC06030), Ministry of Education, Youth and Sports, 2008-2011, V. Sklenař, Masaryk University.
• Wellcome Trust International Senior Research Fellowship in Biomedical Science in Central Europe (067507/Z/02/Z), Welcome Trust, 2003-2007, J. Šponer, Institute of Biophysics AS CR.

SELECTED PUBLICATIONS

• REBLOVA, K., RAZGA, F., LI, W., GAO, H., FRANK, J., SPONER, J. Dynamics of the base of ribosomal A-site finger revealed by molecular dynamics simulations and Cryo-EM. Nucleic Acids Res. 2010, 38(4), p. 1325-1340.
• DITZLER, M., A., OTYEPKA, M., SPONER, J., WALTER, N., G. Conformational and Chemical Change We Can Believe In. Molecular Dynamics and Quantum Mechanics of RNA. Acc. Chem. Res. 2010, 43(1), p. 40-47.
• SPONER, J., RILEY, K., E., HOBZA, P. Nature and magnitude of aromatic stacking of nucleic acid bases. Phys. Chem. Chem. Phys. 2008, 10(19), p. 2595-2610.
• SPONER, J., JURECKA, P., MARCHAN, I., LUQUE, F., J., OROZCO, M., HOBZA, P. Nature of base stacking. Reference quantum chemical stacking energies in ten unique B-DNA base pair steps. Chem. Eur. J. 2006, 12(10), p. 2854-2865.
• SPONER, J., JURECKA, P., HOBZA, P. Accurate interaction energies of hydrogen-bonded nucleic acid base pairs. J. Amer. Chem. Soc. 2004, 126(32), p. 10142-10151.