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+420 541 517 133 |
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| Office: |
Masarykova univerzita - CEITEC MU
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| Phone: |
+420 541 517 246 |
| E-mail: |
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| Office: |
Masarykova univerzita - CEITEC MU
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Research areas
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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
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Studies of canonical and noncanonical DNA molecules
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Quantum chemical modelling of processes relevant to the prebiotic synthesis of nucleic acid components
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Structural bioinformatics of RNA (classification of molecular interactions in nucleic acids based on structural and sequence data)
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Testing and refinement of force fields for atomistic simulations of nucleic acids
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Reference quantum-chemical calculations of molecular interactions and conformational substates in nucleic acids
Main objectives
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Investigation of the role of RNA and DNA in development and human diseases.
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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.
Extended studies will be carried out on selected DNA systems, mainly to understand the role of sequence-dependency of B-DNA structure and the principles of folding of quadruplex DNA.
Prebiotic chemical reactions will be studied using advanced electronic structure computations.
Free energy calculations, or molecular dynamics simulations, often critically depend on the adequacy of the molecular mechanical force fields and other methods describing the relationships 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 focus will be put on noncanonical architectures such as hairpin loops, which are notoriously difficult to describe by the force fields.
CURRENT RESEARCH INFRASTRUCTURE
The laboratory is presently equipped with several computer clusters of different architectures. The newest computer cluster cloud consists of four separate units. The first cluster is composed of 36 nodes with total number of 432 1.9 GHz E5-2420 Xeon cores with 0.8 TB of memory. Second unit dedicated for memory-demanding jobs comprises 12 nodes with 144 1.9 GHz E5-2420 Xeon CPU cores, each one having 96 GB of RAM memory. The third one is a GPU cluster composed of 8 clients with more than 8,000 GPU cores and 48 GB of GDDR5 memory. The last cluster consists of 12 separate nodes each one having 48 AMD Opteron 6238 2.6 GHz CPU cores with more than 60 TB of storage capacity in total. All computing units are interconnected and communicate via a fast Gigabit network operated by a Cisco SG500-52 switch. There are three additional older 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).
1. Multiscale Modeling of Nucleic Acids
Supervisor: prof. RNDr. Jiří Šponer, DrSc.
Consultants:prof. RNDr. Michal Otyepka, Ph.D., Judit Šponerová, PhD.
Annotation:
Nucleic acids (RNA and DNA) belong to the most important biomacromolecules. Studies of structure and dynamics of nucleic acids represent an important task of modern life sciences. Due to fast development of hardware and software, computational and theoretical approaches are frequently used in nucleic acids studies and represent a respected counterpart of experimental techniques. This PhD project will be based on integrated interdisciplinary utilization of a broad spectrum of computational methods (multi-scale modelling) ranging from state-of-the-art quantum-chemical (QM) approaches through modern explicit solvent molecular dynamics (MD) simulation methods up to bioinformatics. Cooperation with established experimental laboratories will provide necessary experimental feedback. State-of-the-art computational facilities are available not only in our laboratory but also in cooperating laboratories abroad. The exact topic will be specified based on the discussion with the applicant and her/his scientific interests and capabilities. Currently available specific themes include for example multiscale studies of protein-RNA complexes, RNA catalysis, structural dynamics and folding of quadruplex DNA and large-scale QM studies of complete nucleic acids building blocks.
2. Experimental and Theoretical Studies of the Origin of Life on the Earth
Supervisor: prof. RNDr. Jiří Šponer, DrSc.
Consultants: Judit Šponerová, PhD.
Annotation:
Formation of the very first oligonucleotide sequences is one of the greatest mysteries surrounding life’s origin. In the last few years experimental and theoretical methods are more and more frequently used to aid experiments at unraveling those simple chemical transformations which could give rise to the emergence of functional biomolecules from an inanimate matter. This PhD project will focus either on the application of modern quantum chemistry and molecular dynamics simulations or on experimental studies to help understanding the abiogenesis of RNA. The research will be carried out using state-of-the-art computational and experimental facilities available in our laboratory and in collaborations with leading experimental laboratories. The exact topic will be specified based on discussion with the applicant and her/his scientific interests and capabilities. Currently available specific themes include for example modelling of (i) chemical mechanisms leading to the prebiotic synthesis of nucleotides, (ii) nonenzymatic template-free oligomerizations, as well as (iii) the emergence of the catalytic activity of short oligonucleotide sequences. The dissertation is suitable for students who are interested in application of modern QM methods and have a feeling for chemical reactions as well as for those who are interested in combining synthetic organic chemistry, biochemistry and analytical chemistry with the aim to reconstruct abiogenesis under laboratory conditions. Purely experimental research is possible, too. Presently, we are involved in studies related for example to the complete experimental reconstruction of a formamide-based pathway to the origin of life, non-templated synthesis of the first RNAs from cyclic nucleotides, origin of the catalytic activity of RNA, the role of photochemical processes in prebiotic chemistry or high energy impact chemistry. Theoretical studies in the topic involve mainly mechanistic investigations, and will be executed using state-of-the-art quantum-chemical (QM) techniques, QM molecular dynamics or classical MD simulations. Experimental work will concentrate on sample preparation and characterization with modern analytical chemistry methods. Because it is a very difficult topic, specific research goal can be proposed only after careful assessment of the capabilities of the applicant. We closely collaborate with other experimental and theoretical laboratories, e.g. E. Di Mauro, R. Salladino, M. Ferus, M. Saitta, J.D. Sutherland and some others.
