Krepl Miroslav, RNDr., Ph.D.
Name: RNDr. Miroslav Krepl, Ph.D.
Education:
- Bachelor’s degree studies – Faculty of Science, Masaryk University, Biochemistry, 2008 – 2011
- Master’s degree studies – Faculty of Science, Masaryk University, Biomolecular chemistry, 2011 – 2013
- D. degree studies – Faculty of Science, Masaryk University, Biomolecular chemistry, 2013 – 2017
Current employment:
- Senior Researcher, Department of structure and dynamics of nucleic acids, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno
- Researcher, Czech Advanced Technology and Research Institute, CATRIN, Palacký University, Olomouc, Czech Republic
Research interests:
My research focuses on study of biologically relevant nucleic acids and proteins by the methods of molecular dynamics (MD) simulations. My primary focus is protein/RNA and protein/DNA complexes.1-21 I am especially interested in biomolecular systems where a significant role of structural dynamics is known or suspected. Although my research is through theoretical methods, I have extensive experience in collaborating with experimental research groups focused on X-ray crystallography, NMR spectroscopy, Cryo-EM, or other biochemical methods.2-8, 13-14, 16-17, 22-27 In addition to practical application of computational methods in biological and biochemical research, I also have experience in developing and benchmarking computational methods.9, 12, 28-34 Apart from protein/RNA and protein/DNA complexes, I have also studied small RNA molecules with prominent roles of non-canonical or recurrent motifs,22, 24, 26-27 and folding pathways of guanine quadruplexes,35-38 I have recently described complete folding pathways of two RRM protein/RNA complexes (HuR RRM3 and SRSF1 RRM2) using a rescaled force field.1
In the near future, the most significant scientific challenge for me will be to apply MD simulations to study folding pathways of diverse protein/RNA complexes and to characterize properties of Holliday Junctions.
References (not a complete list of my publications):
(1) Krepl, Miroslav; Pokorná, Pavlína; Mlýnský, Vojtěch; Stadlbauer, Petr; Šponer, Jiří, Spontaneous Binding of Single-stranded RNAs to RRM Proteins Visualized by Unbiased Atomistic Simulations with a Rescaled RNA Force Field. Nucleic Acids Research 2022, 50, 12480–12496.
(2) Cléry, Antoine; Krepl, Miroslav; Nguyen, Cristina K. X.; Moursy, Ahmed; Jorjani, Hadi; Katsantoni, Maria; Okoniewski, Michal; Mittal, Nitish; Zavolan, Mihaela; Sponer, Jiri; Allain, Frédéric H. T., Structure of SRSF1 RRM1 Bound to RNA Reveals an Unexpected Bimodal Mode of Interaction and Explains its Involvement in SMN1 exon7 Splicing. Nature Communications 2021, 12, 428.
(3) Krepl, Miroslav; Dendooven, Tom; Luisi, Ben F.; Sponer, Jiri, MD simulations reveal the basis for dynamic assembly of Hfq-RNA complexes. Journal of Biological Chemistry 2021, 296, e100656.
(4) Krepl, Miroslav; Damberger, Fred Franz; von Schroetter, Christine; Theler, Dominik; Pokorná, Pavlína; Allain, Frédéric H. T.; Šponer, Jiří, Recognition of N6-Methyladenosine by the YTHDC1 YTH Domain Studied by Molecular Dynamics and NMR Spectroscopy: The Role of Hydration. The Journal of Physical Chemistry B 2021, 125, 7691-7705.
(5) Campagne, Sebastien; Krepl, Miroslav; Sponer, Jiri; Allain, Frederic H. T., Chapter Fourteen - Combining NMR Spectroscopy and Molecular Dynamic Simulations to Solve and Analyze the Structure of Protein–RNA Complexes. In Methods in Enzymology, Wand, A. Joshua, Ed. Academic Press: 2019; Vol. 614, pp 393-422.
(6) Ripin, Nina; Boudet, Julien; Duszczyk, Malgorzata M.; Hinniger, Alexandra; Faller, Michael; Krepl, Miroslav; Gadi, Abhilash; Schneider, Robert J.; Šponer, Jiří; Meisner-Kober, Nicole C.; Allain, Frédéric H.-T., Molecular basis for AU-rich element recognition and dimerization by the HuR C-terminal RRM. Proceedings of the National Academy of Sciences 2019, 116, 2935-2944.
(7) Górecka, Karolina Maria; Krepl, Miroslav; Szlachcic, Aleksandra; Poznański, Jarosław; Šponer, Jiří; Nowotny, Marcin, RuvC Uses Dynamic Probing of the Holliday Junction to Achieve Sequence Specificity and Efficient Resolution. Nature Communications 2019, 10, e4102.
(8) Figiel, Małgorzata; Krepl, Miroslav; Park, Sangwoo; Poznański, Jarosław; Skowronek, Krzysztof; Gołąb, Agnieszka; Ha, Taekjip; Šponer, Jiři; Nowotny, Marcin, Mechanism of Polypurine Tract Primer Generation by HIV-1 Reverse Transcriptase. Journal of Biological Chemistry 2018, 293, 191-202.
(9) Šponer, Jiří; Bussi, Giovanni; Krepl, Miroslav; Banáš, Pavel; Bottaro, Sandro; Cunha, Richard A.; Gil-Ley, Alejandro; Pinamonti, Giovanni; Poblete, Simón; Jurečka, Petr; Walter, Nils G.; Otyepka, Michal, RNA Structural Dynamics as Captured by Molecular Simulations: A Comprehensive Overview. Chemical Reviews 2018, 118, 4177–4338.
(10) Pokorná, Pavlína; Kruse, Holger; Krepl, Miroslav; Šponer, Jiří, QM/MM Calculations on Protein–RNA Complexes: Understanding Limitations of Classical MD Simulations and Search for Reliable Cost-Effective QM Methods. Journal of Chemical Theory and Computation 2018, 14, 5419-5433.
(11) Bochicchio, Anna; Krepl, Miroslav; Yang, Fan; Varani, Gabriele; Sponer, Jiri; Carloni, Paolo, Molecular Basis for the Increased Affinity of an RNA Recognition Motif with Re-engineered Specificity: A Molecular Dynamics and Enhanced Sampling Simulations Study. Plos Computational Biology 2018, 14, e1006642.
(12) Šponer, Jiří; Krepl, Miroslav; Banáš, Pavel; Kührová, Petra; Zgarbová, Marie; Jurečka, Petr; Havrila, Marek; Otyepka, Michal, How to Understand Atomistic Molecular Dynamics Simulations of RNA and Protein–RNA Complexes? Wiley Interdisciplinary Reviews: RNA 2017, 8, e1405.
(13) Figiel, Małgorzata; Krepl, Miroslav; Poznański, Jarosław ; Gołąb, Agnieszka; Šponer, Jiří ; Nowotny, Marcin Coordination between the Polymerase and RNase H Activity of HIV-1 Reverse Transcriptase. Nucleic Acids Research 2017, 45, 3341-3352.
(14) Krepl, Miroslav; Blatter, Markus; Cléry, Antoine; Damberger, Fred F.; Allain, Frederic H.T.; Sponer, Jiri, Structural Study of the Fox-1 RRM Protein Hydration Reveals a Role for Key Water Molecules in RRM-RNA Recognition Nucleic Acids Research 2017, 45, 8046-8063.
(15) Pokorna, P.; Krepl, M.; Kruse, H.; Sponer, J., MD and QM/MM Study of the Quaternary HutP Homohexamer Complex with mRNA, L-histidine Ligand and Mg2+. Journal of Chemical Theory and Computation 2017, 13, 5658–5670.
(16) Konté, Nana Diarra dit; Krepl, Miroslav; Damberger, Fred F; Ripin, Nina; Duss, Olivier; Sponer, Jiri; Allain, Frédéric H.-T., Aromatic Side-chain Conformational Switch on the Surface of the RNA Recognition Motif Enables RNA Discrimination. Nature Communications 2017, 8, e654.
(17) Krepl, Miroslav; Cléry, Antoine; Blatter, Markus; Allain, Frederic H.T.; Sponer, Jiri, Synergy between NMR Measurements and MD Simulations of Protein/RNA Complexes: Application to the RRMs, the Most Common RNA Recognition Motifs. Nucleic Acids Research 2016, 44, 6452-6470.
(18) Estarellas, Carolina; Otyepka, Michal; Koca, Jaroslav; Banas, Pavel; Krepl, Miroslav; Sponer, Jiri, Molecular Dynamic Simulations of Protein/RNA Complexes: CRISPR/Csy4 Endoribonuclease. Biochimica et Biophysica Acta, General Subjects 2015, 1850, 1072-1090.
(19) Krepl, M.; Havrila, M.; Stadlbauer, P.; Banas, P.; Otyepka, M.; Pasulka, J.; Stefl, R.; Sponer, J., Can We Execute Stable Microsecond-Scale Atomistic Simulations of Protein-RNA Complexes? Journal of Chemical Theory and Computation 2015, 11, 1220-1243.
(20) Šponer, Jiří; Banáš, Pavel; Jurečka, Petr; Zgarbová, Marie; Kührová, Petra; Havrila, Marek; Krepl, Miroslav; Stadlbauer, Petr; Otyepka, Michal, Molecular Dynamics Simulations of Nucleic Acids. From Tetranucleotides to the Ribosome. Journal of Physical Chemistry Letters 2014, 5, 1771-1782.
(21) Krepl, Miroslav; Reblova, Kamila; Koca, Jaroslav; Sponer, Jiri, Bioinformatics and Molecular Dynamics Simulation Study of L1 Stalk Non-Canonical rRNA Elements: Kink-Turns, Loops, and Tetraloops. Journal of Physical Chemistry B 2013, 117, 5540-5555.
(22) Vögele, Jennifer; Duchardt-Ferner, Elke; Bains, Jasleen Kaur; Knezic, Bozana; Wacker, Anna; Sich, Christian; Weigand, Julia E; Šponer, Jiří; Schwalbe, Harald; Krepl, Miroslav; Wöhnert, Jens, Structure of an Internal Loop Motif with Three Consecutive U•U Mismatches from Stem–loop 1 in the 3'-UTR of the SARS-CoV-2 Genomic RNA. Nucleic Acids Research 2024, 52, 6687-6706.
(23) Zhang, Zhengyue; Šponer, Jiří; Bussi, Giovanni; Mlýnský, Vojtěch; Šulc, Petr; Simmons, Chad R.; Stephanopoulos, Nicholas; Krepl, Miroslav, Atomistic Picture of Opening–Closing Dynamics of DNA Holliday Junction Obtained by Molecular Simulations. Journal Of Chemical Information And Modeling 2023, 63, 2794–2809.
(24) Voegele, Jennifer; Duchardt-Ferner, Elke; Kruse, Holger; Zhang, Zhengyue; Sponer, Jiri; Krepl, Miroslav; Wohnert, Jens, Structural and Dynamic Effects of Pseudouridine Modifications on Non-canonical Interactions in RNA. Rna-a Publication of the Rna Society 2023, 29, 790-807.
(25) Simmons, Chad R.; MacCulloch, Tara; Krepl, Miroslav; Matthies, Michael; Buchberger, Alex; Crawford, Ilyssa; Šponer, Jiří; Šulc, Petr; Stephanopoulos, Nicholas; Yan, Hao, The Influence of Holliday Junction Sequence and Dynamics on DNA Crystal Self-assembly. Nature Communications 2022, 13, e3112.
(26) Zhang, Zhengyue; Vogele, Jennifer; Mrazikova, Klaudia; Kruse, Holger; Cang, Xiaohui; Wohnert, Jens; Krepl, Miroslav; Sponer, Jiri, Phosphorothioate substitutions in RNA structure studied by molecular dynamics simulations, QM/MM calculations and NMR experiments. Journal of Physical Chemistry B 2021, 125, 825–840.
(27) Krepl, Miroslav; Vögele, Jennifer; Kruse, Holger; Duchardt-Ferner, Elke; Wöhnert, Jens; Sponer, Jiri, An Intricate Balance of Hydrogen Bonding, Ion Atmosphere and Dynamics Facilitates a Seamless Uracil to Cytosine Substitution in the U-turn of the Neomycin-sensing Riboswitch. Nucleic Acids Research 2018, 46, 6528–6543.
(28) Mráziková, Klaudia; Mlýnský, Vojtěch; Kührová, Petra; Pokorná, Pavlína; Kruse, Holger; Krepl, Miroslav; Otyepka, Michal; Banáš, Pavel; Šponer, Jiří, UUCG RNA Tetraloop as a Formidable Force-Field Challenge for MD Simulations. Journal of Chemical Theory and Computation 2020, 16, 7601-7617.
(29) Knappeová, Barbora; Mlýnský, Vojtěch; Pykal, Martin; Šponer, Jiří; Banáš, Pavel; Otyepka, Michal; Krepl, Miroslav, Comprehensive Assessment of Force-Field Performance in Molecular Dynamics Simulations of DNA/RNA Hybrid Duplexes. Journal of Chemical Theory and Computation 2024, 20, 6917-6929.
(30) Mlýnský, Vojtěch; Kührová, Petra; Stadlbauer, Petr; Krepl, Miroslav; Otyepka, Michal; Banáš, Pavel; Šponer, Jiří, Simple Adjustment of Intranucleotide Base-Phosphate Interaction in the OL3 AMBER Force Field Improves RNA Simulations. Journal of Chemical Theory and Computation 2023, 19, 8423-8433.
(31) Fröhlking, Thorben; Mlýnský, Vojtěch; Janeček, Michal; Kührová, Petra; Krepl, Miroslav; Banáš, Pavel; Šponer, Jiří; Bussi, Giovanni, Automatic Learning of Hydrogen-bond Fixes in an AMBER RNA Force Field. Journal of Chemical Theory and Computation 2022, 18, 4490–4502.
(32) Kuhrova, Petra; Mlynsky, Vojtech; Zgarbova, Marie; Krepl, Miroslav; Bussi, Giovanni; Best, Robert B.; Otyepka, Michal; Sponer, Jiri; Banas, Pavel, Improving the Performance of the RNA Amber Force Field by Tuning the Hydrogen-Bonding Interactions. Journal of Chemical Theory and Computation 2019, 15, 3288-3305.
(33) Mladek, Arnost; Krepl, Miroslav; Svozil, Daniel; Cech, Petr; Otyepka, Michal; Banas, Pavel; Zgarbova, Marie; Jurecka, Petr; Sponer, Jiri, Benchmark Quantum-chemical Calculations on a Complete set of Rotameric Families of the DNA Sugar-phosphate Backbone and their Comparison with Modern Density Functional Theory. Physical Chemistry Chemical Physics 2013, 15, 7295-7310.
(34) Krepl, Miroslav; Zgarbová, Marie; Stadlbauer, Petr; Otyepka, Michal; Banáš, Pavel; Koča, Jaroslav; Cheatham, Thomas E.; Jurečka, Petr; Šponer, Jiří, Reference Simulations of Noncanonical Nucleic Acids with Different χ Variants of the AMBER Force Field: Quadruplex DNA, Quadruplex RNA, and Z-DNA. Journal of Chemical Theory and Computation 2012, 8, 2506-2520.
(35) Stadlbauer, Petr; Mlýnský, Vojtěch; Krepl, Miroslav; Šponer, Jiří, Complexity of Guanine Quadruplex Unfolding Pathways Revealed by Atomistic Pulling Simulations. Journal Of Chemical Information And Modeling 2023, 63, 4716-4731.
(36) Islam, Barira; Stadlbauer, Petr; Krepl, Miroslav; Havrila, Marek; Haider, Shozeb; Sponer, Jiri, Structural Dynamics of Lateral and Diagonal Loops of Human Telomeric G-Quadruplexes in Extended MD Simulations. Journal of Chemical Theory and Computation 2018, 14, 5011-5026.
(37) Islam, Barira; Stadlbauer, Petr; Krepl, Miroslav; Koca, Jaroslav; Neidle, Stephen; Haider, Shozeb; Sponer, Jiri, Extended Molecular Dynamics of a C-kit Promoter Quadruplex. Nucleic Acids Research 2015, 43, 8673-8693.
(38) Stadlbauer, Petr; Krepl, Miroslav; Cheatham, Thomas E., III; Koca, Jaroslav; Sponer, Jiri, Structural dynamics of possible late-stage intermediates in folding of quadruplex DNA studied by molecular simulations. Nucleic Acids Research 2013, 41, 7128-7143.