Adam Van Wynsberghe, Physical Chemistry
Office: Taylor Science Center 1063
At Hamilton since 2009
B.A. Ohio Wesleyan University, Biochemistry; Minor: Mathematics, 2001.
Ph.D. University of Wisconsin-Madison with Qiang Cui, Biophysics, 2007.
NIH NRSA Post-Doctoral Fellow at UC-San Diego with J. Andrew McCammon, 2007-2009.
Our lab uses theoretical and computational techniques to investigate the interactions and dynamics of biological macromolecules. We hope to help elucidate the mechanisms by which these marcromolecules utilize intramolecular motion and intermolecular forces to achieve their biological functions. Currently, our main focus has been on exploring the pathways and kinetics of ligands binding to the influenza protein neuraminidase (Figure 1).
Figure 1. Influenza neuraminidase tetramer; active sites
are shown in red, secondary sites are shown in green.
We are currently developing a computational methodology to accurately measure the association rate constants of small ligands to both the active (red in Figure 1) and secondary (green in Figure 1) binding sites. This methodology models the diffusional character of the association pathway using Brownian dynamics (BD) and the local, van der Waal contact search with classical molecular dynamics (MD) simulations. As shown in Figure 2, we are currently attempting to implement this multi-scale method by switching from the approximate BD to the more detailed MD at a proximal elliptical surface. Once the methodology is refined, we hope to deepen our understanding into the binding pathway of small molecules to this important infulenza drug target.
Figure 2. Top (left panel) and side (right panel) view of a neuraminidase monomer. The elliptical surface to switch between BD and MD is shown as partially
transparent. Ligands in atom-type coloring are BD arrivals to the transition surface; ligands in single colors are MD bound to the surface of the protein.
Chemistry 321 Physical Chemistry I
Chemistry 321L Physical Chemistry I Laboratory
Chemistry 322 Physical Chemistry II
Chemistry 120 Principles of Chemistry
Chemistry 120L Principles of Chemistry Laboratory
Chemistry 270L Biological Chemistry Laboratory
XSEDE Allocation: TG-MCB130192, 100,000 Service Units, 2013-2014, PI, A Study of Sialic Acid-Neuraminidase Binding Events through MM/PBSA Free-Energy Calculations. Co-Pi was Hamilton undergraduate Leah Krause '14
National Science Foundation: Major Research Instrumentation, $200,000, 2012-2015, Co-PI, MRI: Acquisition of a High Performance Computer for the Molecular Education and Research Consortium in Undergraduate computational chemistRY (MERCURY)
Research Corporation: Cottrell College Science Award, $35,000 plus $30,000 Hamilton College match, 2010-2012, PI, Accurate Evaluation of Association Rate Constants of Influenza Neuraminidase Inhibitors.
National Science Foundation: Major Research Instrumentation, $177,950, 2010-2012, PI, MRI-R2: Acquisition of a High Performance Computing cluster with a fast interconnect to enable shared-use, college-wide computational investigations at Hamilton College.
Teragrid Allocation: TG-MCB090196, 200,000 Service Units, 2009-2010, PI, Investigations of Ribonuclease A Catalysis.
2012 National Biomedical Computational Resource Summer Institute Scholarship
2008-2009 NIH (NIGMS) Ruth L. Kirschstein NRSA Post-Doctoral Fellowship
2003-2005 National Science Foundation Pre-Doctoral Fellowship
2001 Department of Defense Pre-Doctoral Fellowship (declined)
2001 Honorable Mention, Howard Hughes Medical Institute Pre-Doctoral Fellowship
2001-2002 University of Wisconsin-Madison WARF Prize Fellowship
2001 Slocum Prize in the Sciences (Highest Overall GPA), Ohio Wesleyan University
2001 Outstanding Senior Chemistry Major, Ohio Wesleyan University
2001 Phi Beta Kappa Honor Society, Ohio Wesleyan University
2000 Barry M. Goldwater Scholarship
2000 Ernest B. Yeager Award, Society for Applied Spectroscopy, Cleveland Section
2000 Outstanding Junior Chemistry Major, Ohio Wesleyan University
1999 Outstanding Poster, Central Ohio Undergraduate Research Symposium
1997 National Merit Finalist
(*denotes undergraduate co-author)
Tsutakawa, S. E., A. W. Van Wynsberghe, B. D. Freudenthal, C. P. Weinacht, L. Gakhar, M. T. Washington, Z. Zhuang, J. A. Tainer, and I. Ivanov, 2011. Solution X-ray scattering combined with computational modeling reveals multiple conformations of covalently-bound ubiquitin on PCNA. Proc. Natl. Acad. Sci. 108(43):17672-17677.
Sinko, W., C. de Oliveira, S. Williams, A. Van Wynsberghe, J. Durrant, R. Cao, E. Oldfield, and J. A. McCammon, 2011. Applying Molecular Dynamics Simulations to Identify Rarely Sampled Ligand bound Conformational States of Undecaprenyl Pyrophosphate Synthase, an Antibacterial Target. Chem. Biol. Drug Des. 77(6):412-420.
Van Wynsberghe, A. W. and Q. Cui, 2010. Conservation and Variation of Structural Flexibility in Protein Families. Structure. 18:281-283.
Sung, J. C.*, A. W. Van Wynsberghe, R. E. Amaro, W. W. Li, and J. A. McCammon, 2010. The role of secondary sialic acid binding sites in influenza N1 neuraminidase. J. Amer. Chem. Soc. 132(9):2883-2885.
Van Wynsberghe, A. W., L. Ma, X. Chen, and Q. Cui, 2008. Functional Motions in Biomolecules: Insights from Computational Studies at Multiple Scales. In Computational Structural Biology. T. Schwede and M. Peitsch, editors. World Scientic Publishing.
Kondrashov, D., A. Van Wynsberghe, R. M. Bannen, Q. Cui, and G. N. Phillips, Jr., 2007. Protein Structural Variation in Computational Models and Crystallographic Data. Structure. 15:169-177.
Van Wynsberghe, A., and Q. Cui, 2006. Interpreting correlated motions using normal mode analysis. Structure. 14:1647-1653.
Van Wynsberghe, A. W., and Q. Cui. 2005. Comparison of mode analyses at different resolutions applied to nucleic acid systems. Biophys. J. 89:2939-2949.
Li, G., A. Van Wynsberghe, O. N. A. Demerdash, and Q. Cui. 2005. Normal Mode Analysis of Macromolecules: From Enzyme Active Sites to Molecular Machines. In Normal Mode Analysis: Theory and Applications to Biological and Chemical Systems. Q. Cui and I. Bahar, editors. CRC Press, Boca Raton.
Felitsky, D. J., J. G. Cannon, M. W. Capp, J. Hong, A. W. Van Wynsberghe, C. F. Anderson, and M. T. Record. 2004. The exclusion of glycine betaine from anionic biopolymer surface: Why glycine betaine is an eective osmoprotectant but also a compatible solute. Biochem. 43:14732-14743.
Van Wynsberghe, A., G. H. Li, and Q. Cui. 2004. Normal-mode analysis suggests protein flexibility modulation throughout RNA polymerase's functional cycle. Biochem. 43:13083-13096.
Van Wynsberghe, A. W., S. A. Peebles, R. A. Peebles, and R. L. Kuczkowski. 2000. Rotational spectrum and structure of 1,2-dichloro-3,3,4,4-tetrafluorocyclobutene: Comparison of spectroscopy, diraction, and ab initio results. J. Phys. Chem. A 104:8702-8708.
(*denotes undergraduate co-author)
Alvarado, S. M.*, L. Krause*, A. R. Wu*, and A. W. Van Wynsberghe, 2013. Close-Range Behavior of Oseltamivir with Viral Neueraminidase. Poster- 12th MERCURY Conferencd on Computational Chemistry, Lewisburg, PA.
Banman B. J.*, J. E. Adelman*, A. R. Wu*, and A. W. Van Wynsberghe, 2013. Observing the inter- and intramolecular Evants of Sialic Acid Binding to the Active Site of Neuraminidase. Poster- 12th MERCURY Conferencd on Computational Chemistry, Lewisburg, PA.
Ho, J. H.*, C. M. Montangon*, R. B. Clayton*, and A. W. Van Wynsberghe, 2013. Investigation of the effects of molecular charges and water desolvation on the complex formation of Neuraminidase and its inhibitors. Poster- 12th MERCURY Conferencd on Computational Chemistry, Lewisburg, PA.
O'Grady, C. E.*, P. Talpey*, and A. W. Van Wynsberghe, 2013. Development of a molecular docking exercise to elucidate principles of biophysical chemistry in the general chemistry lab. Poster- 12th MERCURY Conferencd on Computational Chemistry, Lewisburg, PA.
Montagnon, C. M.*, R. B. Clayton*, and A. W. Van Wynsberghe, 2013. Investigation of the effects of electronic desolvation on oseltamivir binding kinetics to N1 influenza neuraminidase. Poster- 245th ACS National Meeting, New Orlenas, LA
Wu, A. R.*, L. Krause*, and A. W. Van Wynsberghe, 2013. Elucidation of the molecular interactions between neuraminidase and sialic acid. Poster- 245th ACS National Meeting, New Orlenas, LA
Van Wynsberghe, A. W., 2012. Simulations of ligand binding pathways: directed diffusion with Hamilton College undergraduates. University of California-San Diego, Modeling Diffusional Encounter and Subsequent Events Mini-Symposium
Van Wynsberghe, A. W., 2012. Hitting the Target: Simulations of the ligand binding pathways of influenza neuraminidase. Colgate University Chemistry Department Seminar Series
Krause, L.*, A. Wu*, D. Mermelstein*, J. E. Adelman*, and A. W. Van Wynsberghe, 2012. The Effect of Starting Location and Orientation on Molecular Dynamics Simulations as Applied to the Influenza Neuraminidase-Sialic Acid System. Poster- 7th National Biomedical Computation Resource Summer Institute, San Diego, CA
Clayton, R. B.*, C. M. Montagnon*, E. L. Losito*, and A. W. Van Wynsberghe, 2012. Investigation of Dierences in Desolvation Energy Between Ligands. Poster- 11th MERCURY conference on Computational Chemistry, Lewisburg, PA
Losito, E. L.*, L. D. Leonard*, and A. W. Van Wynsberghe, 2012. Role of influenza A neuraminidase electrostatics in the binding of ligands. Poster- 243rd ACS National Meeting, San Diego, CA
Mermelstein, D. J.*, J. E. Adelman*, and A. W. Van Wynsbeerghe, 2012. Determination of an Appropriate Surface for the Transition from Brownian Dynamics to Molecular Dynamics in Sialic Acid Binding to Neuraminidase. Poster- 243rd ACS National Meeting, San Diego, CA
Montagnon, C. M.*, L. D. Leonard*, E. L. Losito*, and A. W. Van Wynsberghe, 2012. Investigation of Oseltamivir Binding Kinetics to N1 Influenza Neuraminidase. Poster- 243rd ACS National Meeting, San Diego, CA
Wu, A. R.*, R. S. Green*, and A. W. Van Wynsberghe, 2012. Characterization of the Association between Neuraminidase and Sialic Acid Using Molecular Dynamics Simulations. Poster- 243rd ACS National Meeting, San Diego, CA
UNDERGRADUATE STUDENT THESES SUPERVISED
Carmen M. Montagnon, '13, "Investigation of the Effects of Electronic Desolvation on Oseltamivir Binding Kinetics to N1 Influenza Neuraminidase."
Alvin R. Wu, '13, "Investigating the Favored Binding Paths of Sialic Acid into the Active Site of Neuraminidase."
Erica L. Losito '12, "Role of Neuraminidase Electrostatics in the Binding of Ligands."
Laura D. Leonard '11, "The Role of Secondary Sialic Acid Binding Sites on Avian and Human Influenza Neuraminidases."
Rebecaa S. Green '11, "Identifying Favored Regions of Ligand Interaction Near the Active Site of Neuraminidase."
Carlos A. Rico '10, "The Role of Secondary Sialic Acid Binding Sites on Avian Influenza Neuraminidases."
Thomas Morrell '10, "The Impact of Short Term Dynamics on Ribonuclease A."
Sam H. E. Cho '10, "Conformation Dependence of the Thrombin-Thrombomodulin Interaction."