Vojislava Pophristic PhD
Vojislava Pophristic PhD
Chair, Department of Chemistry & Biochemistry
Professor of Chemistry and Biochemistry
BS (University of Belgrade)
PhD (Rutgers University)
- Molecular Interactions within Biological Systems
- Computational Chemistry
- Inorganic Clusters
Combining ab initio molecular dynamics with accurate quantum chemistry methods to study metal ion solvation.
Using molecular dynamics simulations to investigate heparin binding oligomers.
Research interests of my group focus on the application of computational chemistry methods to study various aspects of biochemical, organic, and inorganic systems. We combine accurate quantum chemistry and ab initio molecular dynamics methods with classical molecular dynamics techniques, which can provide a unique perspective of chemical problems.
The three areas of research to which these computational methodologies are currently being applied, are discussed briefly below.
Solvation and Hydrolysis of Highly-Charged Metal Ions
Using ab initio molecular dynamics in combination with quantum chemistry methods, we investigate the process of solvation, structure and dynamics of solvated ions, as well as small polynuclear species that form upon solvation of heavy metal cations. Metal cations are present in both our environment and living organisms. Important aspects of remediation of polluted soil and water, as well as studying the influence metal ions on our biochemistry rely upon our knowledge of the structures, charges and stabilities of aquated metal cations and their polynuclear hydrolysis products. Due to the limitations inherent to experimental approaches in studying aqueous solutions of heavy metal ions, computational chemistry means, in particular ab initio molecular dynamics, present an advantageous alternative. We currently focus on the solvation chemistry of zirconium, with the long-term goal of developing a broadly effective strategy to tackle the hydrolytic behavior of many strongly-polarizing metal cations important from an industrial, environmental and/or biochemical perspective, providing guidance for the interpretation of existing experimental data, and a basis for the development of new experiments.
Figure: Snapshot from an ab initio molecular dynamics simulation of a Zr(IV) ion (yellow) in aqueous solution, illustrating its solvation shell composition and geometry.
Mechanism of Heparin Binding
Using molecular dynamics simulations, we investigate the mechanism of binding between a pentasaccharide sequence of heparin, proven to be essential for its anticoagulant properties, and a series of synthesized arylamide oligomers, shown to exhibit heparin antidote properties. Heparin is a widely used anticoagulant drug, with undesirable side effects, including excessive bleeding and heparin-induced thrombocytopenia. Our simulations reveal which structural and electronic features are crucial for development of potent arylamide oligomer antidotes.
Figure: An illustration representing the binding mode between heparin (yellow) and an arylamide oligomer (red), a promising heparin antidote.
Force Field Development: Torsional Parameters
We develop force field parameters for synthetic oligomers whose conformational characteristics depend on their intramolecular environment, such as hydrogen bonding. Our current focus is on arylamide oligomers with important biomedical applications. Development of force field parameters, in particular torsional parameters, involves a combination of several computational chemistry techniques (quantum chemistry, ab initio molecular dynamics and classical all-atom molecular dynamics). Our long term goal is to conduct a systematic and thorough theoretical investigation of torsions around single bonds crucial for design of synthetic foldamers that mimic the secondary structures of biopolymers, and thus have a potential for assuming important biochemical functions. The design principles depend heavily on the predictability of oligomer folding, as well as on how tunable and stable the structures are, and thus on our knowledge about the torsions around the oligomer backbone bonds.
Figure: Torsional potential surfaces of dimethyl ether (bottom) and two of its protonated forms (middle and top).
Selected Scholarly Activity
“Mechanistic and Dynamic Insights into Ligand Encapsulation by Helical Arylamide Foldamers” A. M. Abramyan, Z. Liu, V. Pophristic, Phys. Chem. Chem. Phys., 2014, 16, 20406.
“An ab-initio study of pyrrole and imidazole arylamides” A. M. Abramyan, Z. Liu, V. Pophristic, J. Serb. Chem. Soc., 2013, 78, 1789.
“Conformational Preferences of Furan- and Thiophene-based Arylamides: A Combined Computational and Experimental Study” J. F. Galan, C. N. Tang, S. Chakrabarty, Z. Liu, G. Moyna, V. Pophristic, Phys. Chem. Chem. Phys. 2013, 15, 11883.
“An ab initio Molecular Orbital Study of Intramolecular Hydrogen Bonding in Ortho-substituted Arylamides: Implications for the Parameterization of Molecular Mechanics Force Fields”, Z. Liu, A. Teslja, V. Pophristic, J. Comp. Chem. 2011, 32, 1846.
“Intramolecular hydrogen bonding in ortho-substituted arylamide oligomers: A computational and experimental study of ortho-fluoro and ortho-chloro N-methylbenzamides”, J. F. Galan, J. Brown, J. Wildin, Z. Liu, D. Liu, G. Moyna, V. Pophristic, J. Phys. Chem. B 2009, 113, 12809.
“Hydrogen Bonding in ortho-Substituted Arylamides: The Influence of Protic Solvents”, Z. Liu, R. Remsing, D. Liu, G. Moyna, V. Pophristic, letter, J. Phys. Chem. B, 2009, 113, 7041.
“A Computational Study of the Small Zr(IV) Polynuclear Species”, N. Rao, M. N. Holerca, V. Pophristic, J. Chem. Theory Comp., 2008, 4, 145.
“Computational Study of the Zr4+ Tetranuclear Polymer, [Zr4(OH)8(H2O)16]8+”, N. Rao, M. N. Holerca, M. L. Klein, V. Pophristic, J. Phys. Chem. A, 2007, 111, 11395.
I. Ivanov, S. Vemparala, V. Pophristic, K. Kuroda, W. F. DeGrado, M. L. Klein, "Characterization of Non-biological Antimicrobial Polymers in Aqueous Solution and at Water-Lipid Interfaces from All Atom Molecular Dynamics", J. Am. Chem. Soc., 2006, 128, 1778.
V. Pophristic, S. Vemparala, I. Ivanov, Z. Liu, M. L. Klein, W. F. DeGrado, "Controlling the Shape and Flexibility of Arylamides: A Combined Ab Initio, Molecular Dynamics and Classical Molecular Dynamics Study", J. Phys. Chem. B, 2006, 110, 3517.
S. Vemparala, I. Ivanov, V. Pophristic, K. Spiegel,M. L. Klein, "Ab Initio Calculations of Intra-Molecular Parameters for a Class of Arylamide Polymers", J. Comp. Chem., 2006, 27, 693.
S. Vemparala, V. Pophristic, I. Ivanov, M. L. Klein, "Interaction of Arylamide Polymers with Heparin and Lipid Bilayers", Biophys. J., 2005, 88, 235A.
S. Choi, D. J. Clements, V. Pophristic, I. Ivanov, S. Vemparala, J. S. Bennett, M. L. Klein, J. D. Winkler, W. F. DeGrado, "The Design and Evaluation of Heparin-Binding Foldamers", Angew. Chem. Int. Ed., 2005, 41, 6599.
[Note: The figure from the above publication showing the binding of heparin to arylamide, was featured on the cover of this issue of the Journal.]
L. Goodman, H. Gu, V. Pophristic, "Gauche Effect in 1,2-Difluoroethane. Hyperconjugation, Bent Bonds, Steric Repulsion", J. Phys. Chem. A, 2005, 109, 1223.
V. Pophristic, M. L. Klein, M. N. Holerca, "Modeling of Small Aluminum Chlorohydrate Polymers", J. Phys.Chem. A, 2004, 108, 113.
V. Pophristic, M. L. Klein, V. S. K. Balagurusamy, "Structure and Dynamics of Al13O4(OH)24(H2O)12Cl 7, Al13 Polymer", Phys. Chem. Chem. Phys., 2004, 6, 919.
L. Goodman, V. Pophristic, "Ethane Prefered Conformation", in The Encyclopedia of Nanoscience and Nanotechnolgy, J. A. Schwartz, Ed., Marcel Dekker, New York, 2004.
V. Pophristic, L. Goodman, "Influence of Intramolecular Interactions on Gearing and Antigearing Torsional Motions", J. Phys. Chem. A, 2003, 107, 3538.
V. Pophristic, L. Goodman, L. Gorb, J. Leszczynski, "Acetone n-Radical Cation Conformational Preference and Torsional Barrier", J. Chem. Phys., 2002, 116, 7049.
V. Pophristic, L. Goodman, "Origin of Staggered Conformational Preference in Methanol", J. Phys. Chem., 2002, 106, 1642.
V. Pophristic, L. Goodman, "Hyperconjugation Not Steric Repulsion Leads to the Staggered Structure of Ethane", Nature, 2001, 411, 565.
V. Pophristic, L. Goodman, "Exchange Repulsion Increases Internal Rotation Floppiness", J. Chem. Phys, 2001, 115, 5132.
V. Pophristic, L. Goodman, C. Wu, "Disilane Internal Rotation", J. Phys. Chem. A, 2001, 105, 7454.
V. Pophristic, L. Goodman, "Influence of Protonation on the Internal Rotation of Dimethyl Ether", J. Phys. Chem. A, 2000, 104, 3231.
L. Goodman, V. Pophristic, F. Weinhold, "Origin of Internal Rotation Barriers", Acc. Chem. Res., 1999, 32, 983.
L. Goodman, V. Pophristic, "Rotational Barriers", in The Encyclopedia of Computational Chemistry, P.v.R Schleyer, Ed., volume 4, p. 2525, John Wiley & Sons, Chichester, 1998.
V. Pophistic, L. Goodman, N. Guchhait, "Role of Lone-Pairs in the Internal Rotation Barriers", J. Phys. Chem., 1997, 101, 4290.
V. Torbica (Torbica-Pophristic), and M. Peric, "Ab Initio Investigation of the Vibronic Structure of the B3Σu-, 23Σu- → X3Σg- Spectral System of the Oxygen Molecule", J. Serb. Chem. Soc., 1994, 59, 473.
|Office location:||Griffith Hall Room 140A|
|Mailing address:||Box 43|
University of Sciences
600 South 43rd Street
Philadelphia, PA 19104-4495
v [dot] pophri [at] usciences [dot] edu