What molecular properties give rise to a strong piezoelectric response?

  • By Burcu Ozden
  • 22 November 2017

In this study Geoffrey R. Hutchison and his colleagues tried to answer the question of " What molecular properties give rise to a strong piezoelectric response?"  To do so, they systematically probe the interplay among peptide chemical structure, folding propensity, and piezoelectric properties, uncovering in the process new insights into the origin of peptide electromechanical response. They have designed variety of peptides and peptoids and test the effect of molecular properties on piezoelectric response via serious measurements including ircular dichroism (CD), Polarization-modulated infrared reflection−absorption spectroscopy (PM-IRRAS), tomic force microscopy (AFM), piezo-force microscopy (PFM), and X-ray photoelectron spectroscopy (XPS) measurements. They showed backbone rigidity is an important determinant in peptide electromechanical responsiveness. 

Chemical Theory, Models and Computational Methods (CTMC)

  • By Aude Marjolin
  • 29 August 2016

The program supports the discovery and development of theoretical and computational methods or models to address a range of chemical challenges, with emphasis on emerging areas of chemical research. Proposals that focuson established theoretical or computational approaches should involve innovative additions or modifications that substantially broaden their applicability.

Areas of interest include, but are not limited to, electronic structure, quantum reaction dynamics, statistical mechanics, molecular dynamics, and simulation and modeling techniques for molecular systems and systems in condensed phases. Areas of application span the full range of chemical systems from small molecules to mesoscopic aggregates, including single molecules, biological systems and materials in condensed phases.

Department of Chemistry, University of Pittsburgh
Ph.D., Biophysics, University of California San Francisco, 2002

Our research is focused on the use of molecular simulations to characterize the free energy landscapes and kinetics of a variety of biological processes, including large protein conformational transitions and protein binding. We have also been developing simulation strategies for aiding the design of protein-based conformational switches. Finally, we are developers of an upcoming AMBER force field and, a freely available, highly scalable software implementation of weighted ensemble path sampling strategies for the simulation of rare events (e.g. protein folding and protein binding).

Our research falls into the following main areas:

1) Development of weighted ensemble path sampling strategies and software for the efficient sampling of rare events (e.g. protein folding and binding) with rigorous kinetics.

2) Application of molecular simulations to investigate the mechanisms of protein conformational transitions, binding, and assembly processes.

3) Development of molecular simulation strategies for aiding the design of protein conformational switches.

4) Development of biomolecular force fields.

Selected Publications: 
  • "Weighted Ensemble Simulation: Review of Methodology, Applications, and Software (Review)," Zuckerman, D.M.Chong, L.T., Annual Review of Biophysics 46, 43 (2017)
  • "Path-sampling strategies for simulating rare events in biomolecular systems," Chong, L.T., Saglam, A.S., Zuckerman, D.M., Current Opinion in Structural Biology 43, 88, (2017)  
  • "Efficient Atomistic Simulation of Pathways and Calculation of Rate Constants for a Protein-Peptide Binding Process: Application to the MDM2 Protein and an Intrinsically Disordered p53 Peptide," Zwier, M.C., Pratt, A.J., Adelman, J.L., Kaus, J.W., Zuckerman, D.M., Chong, L.T., J. Phys. Chem. Lett 7, 3440 (2016)
  • "Further along the Road Less Traveled: AMBER ff15ipq, an Original Protein Force Field Built on a Self-Consistent Physical Model," Debiec, K.T., Cerutti, D.S., Baker, L.R., Gronenborn, A.M., Case, D.A., Chong, L.T., J. Chem. Theory Comput. 12, 3926 (2016)
  • "Highly Efficient Computation of the Basal kon using Direct Simulation of Protein-Protein Association with Flexible Molecular Models," Saglam, A.S., Chong, L.T., J. Phys. Chem. B 120, 117 (2016)
Most Cited Publications
  1. "Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models"  Kollman, P.A., Massova, I., Reyes, C., (...), Case, D.A., Cheatham III., T.E. Accounts of Chemical Research
  2. "The Amber biomolecular simulation programs" Case, D.A., Cheatham III, T.E., Darden, T., (...), Wang, B., Woods, R.J. Journal of Computational Chemistry 26(16), pp. 1668-1688
  3. "GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit" Kollman, P.A., Massova, I., Reyes, C., (...), Case, D.A., Cheatham III., T.E. Accounts of Chemical Research
  4. "Docking and scoring in virtual screening for drug discovery: Methods and applications" Kitchen, D.B., Decornez, H., Furr, J.R., Bajorath, J. 2004 Nature Reviews Drug Discovery
  5. "Exploring Protein Native States and Large-Scale Conformational Changes with a Modified Generalized Born Model" Onufriev, A., Bashford, D., Case, D.A. Proteins: Structure, Function and Genetics
Recent Publications
  1. "Evaluating the Strength of Salt Bridges: A Comparison of Current Biomolecular Force Fields,"  K T Debiec, A M Gronenborn, and L T Chong Journal of Physical Chemistry B 123.19 (2019)
  2. "Large enhancement of response times of a protein conformational switch by computational design,"  Alex J. DeGrave, Jeung-Hoi Ha, Stewart N. Loh & Lillian T. Chong, Nature Commnications, 9, 1013 (2018).
  3. "Integrating NMR, SAXS, and Atomistic Simulations: Structure and Dynamics of a Two-Domain Protein." Debiec, K.T., Whitley, M.J., Koharudin, L.M.I., Chong, L.T., Gronenborn, A.M.     Biophysical Journal 114(4), pp. 839-855. (2018).
  4. "WESTPA 2.0 Advances in Sampling, Storage, and Analysis of Weighted Ensemble Simulations,"  AJ Pratt, D M Zuckerman, and L T ChongBiophysical Journal 114.3 (2018)
  5. "Links between the charge model and bonded parameter force constants in biomolecular force fields." Cerutti, D.S., Debiec, K.T., Case, D.A., Chong, L.T.     Journal of Chemical Physics 147(16),161730. (2017).
Department of Chemistry and Biochemistry, Duquesne University
Ph.D., Computational and Theoretical Organic Chemistry, UCLA, 1990

Our research program is driven by significant problems in organic, biochemistry, and physical chemistry. Our research in chemical theory and computation is fully integrated in strong collaboration with successful experimental chemists. We have a full range on interests, starting with the development of fundamental ideas on the theory of chemical bonding, and how this information can be used to understand the fundamentals of Lewis acidity and basicity, organic reaction catalysis, organometallic structures, and the bonding and reactions at surfaces. In the field of biochemistry, we investigate the energetics and mechanisms of phosphoryl transfer reactions, and design new antimicrobial agents to light the increasing risk of drug resistant bacterial fungal infections.

Selected Publications: 
  • "Metalated nitriles: SNi′ cyclizations with a propargylic electrophile," Ping Lu, Venkata S. Pakkala, Jeffrey D. Evanseck, Fraser F. Fleming, Tetrahedron Letters 56, 3216 (2015)
  • "Intramolecular Charge-Assisted Hydrogen Bond Strength in Pseudochair Carboxyphosphate," Sarah E. Kochanek, Traci M. Clymer, Venkata S. Pakkala, Sebastien P. Hebert, Kyle Reeping, Steven M. Firestine, and Jeffrey D. Evanseck, J. Phys. Chem. B 119, 1184 (2015)
  • "Common Hydrogen Bond Interactions in Diverse Phosphoryl Transfer Active Sites," Jean C. Summerton, Gregory M. Martin, Jeffrey D. Evanseck, Michael S. Chapman, PLOS One 9, e108310 (2014)
  • "Hyperconjugation-Mediated Solvent Effects in Phosphoanhydride Bonds," Jean C. Summerton, Jeffrey D. Evanseck, and Michael S. Chapman, J. Phys. Chem. A 116 10209 (2012)
Most Cited Publications
  1. "All-atom empirical potential for molecular modeling and dynamics studies of proteins," A. D. MacKerell Jr., D. Bashford, M. Bellott, R. L. Dunbrack Jr., J. D. Evanseck, M. J. Field, S. Fischer, J. Gao, H. Guo, S. Ha, D. Joseph-McCarthy, L. Kuchnir, K. Kuczera, F. T. K. Lau, C. Mattos, S. Michnick, T. Ngo, D. T. Nguyen, B. Prodhom, W. E. Reiher, B. Roux, M. Schlenkrich, J. C. Smith, R. Stote, J. Straub, M. Watanabe, J. Wiórkiewicz-Kuczera, D. Yin, and M. Karplus, J. Phys. Chem. B. 102, no. 18 (1998)
  2. "Transition structures of hydrocarbon pericyclic reactions," Houk, Kendall N., Yi Li, Jeffrey D. EvanseckAngewandte Chemie International Edition 31, no. 6 (1992)
  3. "Locally accessible conformations of proteins: multiple molecular dynamics simulations of crambin," Caves, Leo SD, Jeffrey D. Evanseck, Martin Karplus.,  Protein Science 7, no. 3 (1998)
  4. "Influence of the heme pocket conformation on the structure and vibrations of the Fe-CO bond in myoglobin: a QM/MM density functional study," Rovira, Carme, Brita Schulze, Markus Eichinger, Jeffrey D. Evanseck, Michele Parrinello,  Biophysical journal 81, no. 1 (2001)
  5. "Density functional theory study of aqueous-phase rate acceleration and endo/exo selectivity of the butadiene and acrolein Diels-Alder reaction," Kong, S., Evanseck, J.D., Journal of the American Chemical Society 122, no. 42 (2000)
Recent Publications
  1. "Chemistry REU Leadership Group: Support for the Chemistry Undergraduate Research Community"  Watkins, L.M., Evanseck, J.DACS Symposium Series 1295, pp. 73-83
  2. "Evolution of an AwESOME Chapter"  Cooper, E., Shaik, S., Bautista, D., (...), Gawalt, E.S., Evanseck, J.D. ACS Symposium Series 1278, pp. 55-71
  3. "Metalated nitriles: SNi′ cyclizations with a propargylic electrophile," Ping Lu, Venkata S. Pakkala, Jeffrey D. Evanseck, Fraser F. Fleming, Tetrahedron Letters 56, 3216 (2015)
  4. "Intramolecular Charge-Assisted Hydrogen Bond Strength in Pseudochair Carboxyphosphate," Sarah E. Kochanek, Traci M. Clymer, Venkata S. Pakkala, Sebastien P. Hebert, Kyle Reeping, Steven M. Firestine, and Jeffrey D. Evanseck, J. Phys. Chem. B 119, 1184 (2015)
  5. "Common Hydrogen Bond Interactions in Diverse Phosphoryl Transfer Active Sites," Jean C. Summerton, Gregory M. Martin, Jeffrey D. Evanseck, Michael S. Chapman, PLOS One 9, e108310 (2014)
Personal | Department
Department of Chemistry and Biochemistry, Duquesne University
Ph.D., Physical Chemistry, Purdue University, 1985

Research in the laboratory consists of the development and application of computational methods in collaboration with experimental research laboratories. Our research interests fall into the areas of computational biophysics and computational material sciences.

Some our current research projects involve, studying the transport mechanism of neurotransmitter sodium symporter proteins, where we are simulating in vivo conditions using molecular dynamics simulations to observe changes in conformation of proteins upon substrate transport. We are researching computer-aided drug design by applying free energy calculations to elucidate intermolecular interactions of various substrates and inhibitors with monoamine transporters. We are investigating conformational properties of polyglutamine peptide systems by applying molecular dynamics, using the metadynmics sampling algorithm, to explore the conformational free energy landscape of polyglutamine peptides in solvent. We are involved in the electronic structure calculations of extended solids, where we are applying computational methods to investigate and predict physicochemical properties of materials. We are also studying smart materials such as hydrogels of PNIPAM.

In the past, we have studied antifreeze proteins at ice/water interfaces and interaction of N-acetylglucosamine with chitnase. The folding of small peptides in salt solution, and structure, function, and dynamics of monoamine transporters have been studied as well.

Dr. Madura is also one of the primary authors to the Brownian dynamics program UHBD, which is used to calculate the diffusion-controlled rate-constants for biomolecular encounters.

Most Cited Publications
  1. "Comparison of simple potential functions for simulating liquid water," William L. Jorgensen, Jayaraman Chandrasekhar, and Jeffry D. Madura, Roger W. Impey and Michael L. Klein, J. Chem. Phys. 79, 926 (1983)
  2. "Optimized intermolecular potential functions for liquid hydrocarbons," William L. Jorgensen, Jeffry D. Madura, Carol J. Swenson, J. Am. Chem. Soc. 106, 6638 (1984)
  3. "Development of an improved four-site water model for biomolecular simulations: TIP4P-Ew," Hans W. Horn, William C. Swope, and Jed W. Pitera, Jeffry D. Madura and Thomas, J. Dick Greg, L. Hura, Teresa Head-Gordon, J. Chem. Phys.120, 9665 (2004)
  4. "Temperature and size dependence for Monte Carlo simulations of TIP4P water," William L. Jorgensen & Jeffry D. MaduraMolecular Physics 56, 1381 (1985)
  5. "Electrostatics and diffusion of molecules in solution: simulations with the University of Houston Brownian Dynamics program," Jeffry D. Madura, James M. Briggs, Rebecca C. Wade, Malcolm E. Davis, Brock A. Luty, Andrew Ilin, Jan Antosiewicz, Michael K. Gilson, Babak Bagheri, L.Ridgway Scott, J.Andrew McCammon, Computer Physics Communications 91, 57 (1995)
Recent Publications
  1. "Polyglutamine Fibrils: New Insights into Antiparallel β-sheet Conformational Preference and Side Chain Structure," David Punihaole, Riley J Workman, Zhenmin Hong, Jeffry D Madura, Sanford A Asher, J. Phys. Chem. B 120, 3012 (2016)
  2. "2-Substituted 3β-Aryltropane Cocaine Analogs Produce Atypical DAT Inhibitor Effects Without Inducing Inward-Facing DAT Conformations," Weimin C. Hong, Theresa A. Kopajtic, Lifen Xu, Stacey A. Lomenzo, Bernandie Jean, Jeffry D. Madura, Christopher K. Surratt, Mark L. Trudell and Jonathan L. Katz, J Pharmacol Exp Ther 356, 624 (2016)
  3. "Human alpha1 Glycine Receptor Allostery as Identified by State-Dependent Crosslinking Studies," Michael Cascio, Rathna J Veeramachaneni, Jeffry MaduraBiophysical Journal 110, 201a (2016)
  4. "Crosslinking/MS Studies of Cholesterol Interactions with Human alpha1 Glycine Receptor," Nicholas Ferraro, Emily Benner, Jeffry Madura, Michael Cascio, Biophysical Journal 110, 355a (2016)
  5. "Computational Investigation of the Transport Mechanism of Neurotransmitter Sodium Symporters using a Physiological Ion Gradient," Emily M Benner, Jeffry D MaduraBiophysical Journal 3, 626a (2016)