Vojislava Pophristic PhD
Vojislava Pophristic PhD
Chair, Department of Chemistry & Biochemistry
Professor of Chemistry and Biochemistry
BS, Physical Chemistry, University of Belgrade, Serbia
PhD, Chemistry, Rutgers University, New Brunswick, New Jersey
Postdoctoral Fellow, University of Pennsylvania
Our group develops and uses computational tools to study structures and dynamics of chemical entities that mimic 3D motifs found in biomolecules. The group also works on computational design of oligomers for therapeutic applications.
Computationally Aided Rational Design of Foldamers
Our research group has been developing an approach that allows structure predictability of an important class of foldamers, oligomers that fold into well-defined secondary structures in solution, and have potential in a variety of novel applications. The main objective of the work is to modify computational tools for accurate prediction of foldamer structures, and to establish information transferability between the foldamer building blocks and the final foldamer structure.
The group focuses on arylamide foldamers, and has developed an approach that takes into consideration specific foldamer building block effects and non-covalent interactions between adjacent monomers that are crucial for arylamide foldamer structure control, i.e. for conformational properties at the oligomer level. This approach has been applied to several systems, described below.
Applications of the Computationally Aided Design of Foldamers
A variety of novel ‘‘apple peel’’ shaped helical arylamide capsules have been experimentally pursued due to their flexible nature and designability. We have been working on already known systems, as well as possible modifications of the capsules. For example, using molecular dynamics simulations with our new aryl-amide force field parameters, we identified ligand binding/release mechanisms for a class of arylamide capsules, in which the capsule’s helical structure is either minimally disturbed or restored quickly. Furthermore, we determine the effects of ligand sizes, their chemical nature (hydrogen bonding capabilities), and solvents on capsule binding modes and stabilities.
Foldamer Helix Handedness Inversion
Handedness of helical molecules affects both their structure and function. Handedness inversion of helical arylamides is of particular interest to our group due to its role in revealing information on the stability of helix structures and in the design of helical capsules for diastereoselective encapsulation of chiral ligands. Various aspects of foldamer handedness inversion have been examined by experimental methods, facilitating our work. We study handedness inversion mechanism using metadynamics method and our modified force field parameters, with the goal of obtaining the free energy of handedness. So far, we have demonstrated that, to change their handedness, arylamide helices do not need to fully unfold; rather, they go through a stepwise pathway, where each step consists of a previously unfolded dihedral angle folding into the opposite handedness, and its adjacent dihedral angle unfolding in preparation for the next step.
DNA Binding of Cyclic Polyamides
Polyamides have been experimentally designed to sequence-specifically bind to the DNA minor groove and disrupt protein-DNA interactions of medically important transcription factors, influencing thus their overexpression, a distinguishing feature of many types of cancers. Using our computational approach, we address how dynamic perturbations of DNA grooves and DNA bending upon ligand binding influence conformational flexibility in both the double helix and polyamides, and what roles various features of polyamides play in the binding.
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 this 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