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Ivaylo Nikolaev Ivanov

Ivaylo Nikolaev Ivanov Ivaylo Nikolaev Ivanov
Assistant Professor


B.S. (1996):  Sofia University "St. Kliment Ohridski", Sofia, Bulgaria
M.S. (1999) :  Carnegie Mellon University, Pittsburgh, PA
Ph.D. (2004) :  University of Pennsylvania, Philadelphia, PA
Postdoctoral Scholar, Chemistry- (2005-2009) :  University of California, San Diego and the Scripps Research Institute, La Jolla, CA

Dr. Ivaylo Nikolaev Ivanov
Department of Chemistry
Georgia State University
P.O. Box 4098
Atlanta, Georgia 30302-4098

Phone: 404-413-5529
Lab Phone: 404-413-5552
Fax: 404-413-5505
Office: 515 Science Annex
Email:  cheini@langate.gsu.edu

The Ivanov Research group site.

Research Interests

The research in our group focuses on realistic, first-principles simulations of key biological processes of relevance to DNA replication and repair and centers on the following three areas.

Molecular description of archaeal and eukaryotic clamp loading. Proliferating cell nuclear antigen (PCNA) is a toroidal-shaped protein (sliding clamp) that can encircle and slide along DNA. By tethering polymerases to DNA, it ensures processive replication. PCNA plays a pivotal role in DNA replication, modification and repair by coordinating the ordered exchange of repair enzymes and intermediates at the replication fork. To perform its vital functions, the clamp has to be opened and resealed at DNA primer-template junctions by the action of the clamp loader ATPase RFC. Understanding the mechanism of this process constitutes a significant piece in the puzzle of processive DNA replication. Our research aims to provide a unified molecular-level description of prokaryotic, archaeal and eukaryotic clamp loading that would account for all experimental observations available to date.

Conformational switching and exchange of repair enzymes bound to PCNA. In addition to its function as a polymerase accessory factor, PCNA is a recognized master coordinator of cellular responses to DNA damage. Thus, it is of great interest to examine the reversible associations of DNA repair proteins with PCNA and the conformational switching leading to exchange of repair intermediates. Specifically, we will focus on the interactions of flap endonuclease-1 (FEN-1) and DNA ligase 1 (Lig-1) with PCNA and DNA in the context of a proposed handoff mechanism for DNA repair enzymes at the PCNA locus. Groundbreaking structural biology work has opened up the possibility of investigating these large supramolecular assemblies in atomic detail. A modular multi-scale approach will be adopted wherein the individual components of the assembly are first studied by atomistic simulations, followed by construction of lower resolution (coarse grain) models for the complexes. The models could be instrumental in contributing testable hypotheses and directing future experimental efforts in this exciting research area.

Enzyme participants in base excision repair. As a third research thrust, we explore the catalytic repertoire of the enzyme participants in the base excision repair (BER) pathway – a major contributor to genomic integrity in cells. Rationalizing the origins of the remarkable catalytic power of enzymes has been a long-standing challenge for both experimental and theoretical chemical biology. Advances on the theoretical front have been based on the advent of quantum mechanics molecular mechanics (QM/MM) methods. More recently these have been coupled to ab initio molecular dynamics (AIMD) techniques, which have made possible the introduction of dynamical, many-body and polarization effects into simulation models of unprecedented size and sophistication. I will apply state-of-the-art AIMD methodologies to elucidate the origin of the catalytic power of enzymes involved in DNA replication and repair. Detailed mechanistic analysis would reveal the origins of damage recognition and selectivity in these systems. In practical terms, this research has the potential to aid in the development of enzyme inhibitors and thus has direct relevance to drug design. Ultimately, the scope of this research will be expanded to encompass all steps in base excision repair – from the damage specific action of DNA glycosylases, to the final repair step carried out by DNA ligase.

In summary, the research outlined herein is aimed at addressing critical problems in the biomedical arena and unified by the common theme of how cells accomplish faithful duplication of their genetic material. Specifically, the research plan has direct bearing on understanding the molecular basis of genetic integrity and the loss of this integrity in cancer and in degenerative diseases.

Publications

  1.   van Wynsberghe, A.*; Ivanov*, I.; Tainer, J.A.; McCammon J.A. Multi-scale modeling of  PCNA - monoubiquitin interactions (in preparation)

  2.  Ivanov, I.; Tainer, J. A.; McCammon, J. A. Specific recognition of the ring-opened state of proliferating cell nuclear antigen by replication factor C promotes eukaryotic clamp-loading (submitted)

  3. Cheng, X.; Ivanov, I.; Hailong, W.; Sine, S. M.; McCammon, J. A. Molecular dynamics simulations of ELIC - a prokaryotic homologue of the nicotinic acetylcholine receptor Biophysical Journal 2009, 96, 4502–4513

  4. Amaro, R. E.; Cheng, X.; Ivanov, I.; Xu, D.; McCammon, J.A. Characterizing loop dynamics and
    ligand recognition in human- and avian-type influenza neuraminidases via generalized born molecular
    dynamics and end-point free energy calculations    . Journal of the American Chemical Society 2009,
    131, 4702-4709

  5. Som A.; Vemparala S.; Ivanov I.; Tew G. N. Synthetic mimics of antimicrobial peptides. Peptide
    Science (Biopolymers) 2008, 90, 83-93.

  6. Gorfe, A. A.; Chang, C. A.; Ivanov, I.; McCammon, J. A.Dynamics of the Acetylcholinesterase Tetramer Biophysical Journal 2007, 94, 1144-1154.

  7. Ivanov, I.; Cheng, X.; Sine, S. M.; McCammon, J. A. Barriers to Ion Translocation in Cationic and Anionic Receptors from the Cys-Loop Family Journal of the American Chemical Society 2007 129 8217-8224

  8. Cheng, X.; Ivanov, I.; Wang, H.; Sine, S. M.; McCammon, J. A. Nanosecond Time Scale Conformational Dynamics of the Human alpha7 Nicotinic Acetylcholine Receptor Biophysical Journal 2007 127doi:10.1529/biophysj.107.109843

  9. Ivanov, I.; Tainer, J. A.; McCammon, J. A. Unraveling the three-metal-ion catalytic mechanism of the DNA repair enzyme endonuclease IV
    Proceedings of the National Academy of Sciences U.S.A. 2007 , 104,1465-70

  10. Ivanov, I.; Chapados B.; McCammon, J. A.;Tainer, J. A. Proliferating cell nuclear antigen loaded onto double-stranded DNA: dynamics, minor groove interactions and functional implications
    Nucleic Acids Research 2006 34, 6023-33.

  11. Ivanov, I; Vemparala, S.; Pophristic, V.; Kuroda, K.; DeGrado, W. F.; McCammon, J.A.; Klein, M. L. Characterization of non-biological antimicrobial polymers in aqueous solution and at water-lipid interfaces Journal of the American Chemical Society 2006 128, 1778-1779.

  12. Vemparala, S.; Ivanov, I.; Pophristic, V.; Spiegel, K.; DeGrado, W. F.; Klein, M. L. Ab initio calculations of intra bond parameters for a class of arylamide polymers Journal of Computational Chemistry 2006 27, 693.

  13. Pophristic, V.; Vemparala, S.; Ivanov, I.; Liu, Z.; Klein, M. L.; DeGrado, W. F. Controlling the shape and flexibility of arylamides: a combined ab initio, ab initio molecular dynamics and classical molecular dynamics study Journal of Physical Chemistry B 2006 110, 3517-3526.

  14. Ivanov, I.; Raugei, S.; Chen, B.; Klein, M. L. Relative pKa values from first-principles molecular dynamics: the case of histidine deprotonation Journal of Physical Chemistry B 2006 110, 6365-

  15. Choi, S.; Clements, D. J.; Pophristic, V.; Ivanov, I.; Vemparala, S.; Bennett, J. S.; Klein, M. L.; Winkler, J. D.; and DeGrado, W. F. The Design and Evaluation of Heparin-Binding Foldamers Angewandte Chemie-International Edition 2005 

  16. Ivanov, I. and M. L. Klein Dynamical flexibility and proton transfer in the arginase active site probed by ab initio molecular dynamics methods Journal of the American Chemical Society 2005 127, 4010-4020

  17. Nielsen, S. O. ; Lopez, C. F. ; Ivanov, I. ; Moore, P. B. ; Shelley, J. C. ; Klein, M. L. Transmembrane peptide induced lipid sorting and mechanism of L- alpha to inverted phase transition using coarse grain molecular dynamics Biophysical Journal 2004 87, 2107-2115

  18. Chen, B. ; Ivanov, I. ; Klein, M. L. ; Parrinello, M. Hydrogen bonding in water  Physical Review Letters 2003 91, 215503

  19. Ivanov, I.; Klein, M. L. First Principles Computational Study of the Active Site of Arginase Proteins: Structure, Function, and Bioinformatics 2004 54, 1-7

  20. Min, G. et al. Solution characterization of monodisperse atactic polystyrenes by static and dynamic light scattering International Journal Of Polymer Analysis And Characterization 2003 (accepted)

  21. Ivanov, I. ; Klein, M. L. Deprotonation of a histidine residue in aqueous solution using constrained ab initio molecular dynamics  Journal of the American Chemical Society 2002 124, 13380-13381

  22. Chen, B. ; Ivanov, I. ; Park, J. M. ; Parrinello, M. ; Klein, M. L.  Solvation structure and mobility mechanism of OH-: A Car- Parrinello molecular dynamics investigation of alkaline solution Journal of Physical Chemistry B  2002 106, 12006-12016

  23. Chen, B. ; Park, J. M. ; Ivanov, I. ; Parrinello, M. ; Klein, M. L. First-principles study of aqueous hydroxide solutions Journal of the American Chemical Society 2002 124, 8534-8535.

  24. Ivanov, I., Gherman, B. F. & Yaron, D. Comparison of the INDO band structures of polyacetylene, polythiophene, polyfuran, and polypyrrole Synthetic Metals 2001 116, 111-114.

 

Curriculum Vitae