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Department of Chemistry
101 N. Merion Ave
Bryn Mawr, PA 19010
610-526-7392, or
Fax: 610-526-5086

Judith M. LaLonde

The focus of my research program is computational chemistry and molecular modeling to design small molecule inhibitors of disease relevant protein targets.   I am former protein crystallographer with training in computational chemistry.  In addition I have several years experience in structure based drug design in the pharmaceutical industry.  I currently direct a modeling core for a HIV NIH PO1 consortium collaborating with virologists, synthetic, biophysical and peptide chemists and protein crystallographers. The major focus of the modeling is to discover compounds that inhibit the binding of the HIV viral glycoprotein, gp120, to the host cell receptor, CD4, thus blocking HIV cell entry and infection.  Crystal structures of the gp120-CD4 complex are used in concert with several computational approaches: binding mode prediction by docking, virtual screening with ligand shape-based matching methods, and molecular dynamics and the Gaussian Network Model to explore protein dynamics.   A virtual screening protocol was used to identify and synthesize over 75 analogues of a small molecule inhibitor of gp120-CD4 binding.

A second focus of modeling is Indoleamine 2, 3-Dioxygenase (IDO), a regulator of the immune system and a target for anti-cancer therapy.   In concert with the Prendergast team at Lankenau Institute of Medical Research (LIMR), and Prof. Malachowski at Bryn Mawr College, computational approaches are used to design and optimize IDO inhibitors.  Applying structure-based design methods with an IDO crystal structure has resulted in enhancements to several IDO inhibitor compound classes. 

gnm min max

Gaussian Network Model Fluctuation Minima (Blue) and Maxima (Green) in the HIV glycoprotein, gp120

Recent Publications

“Design, Synthesis and Biological Evaluation of Small Molecule Inhibitors of CD4-gp120 Binding Based on Virtual Screening”, Judith M. LaLonde, Mark Elban, Joel R. Courter, Akihiro Sugawara, Toyoharu Kobayashi, Takahiro Soeta, Danny Ng, Navid Madani, Amy M. Princiotto, Young Do Kwon, Peter D. Kwong, Arne Schon, Ernesto Freire, Joseph Sodroski, Amos B. Smith III,  Bioorganic Medicinal Chemistry, Accepted

“Some Drug Properties are Dependent on Thermodynamic Signature” Chemical Biology & Drug Design", Arne Schön, Navid Madani, Amos B. Smith, III, Judith M. Lalonde and Ernesto Freire Accepted

“Fluctuation Dynamics Analysis of gp120 Envelope Protein Reveals a Topologically Based Communication Network”, Indira Shrivastava and Judith LaLonde,PROTEINS: Structure, Function, and Bioinformatics. 2010 78: 2935–2949. doi: 10.1002/prot.22816.

“Active Core in a TriazolePeptide Dual Site Antagonist of HIV-1 gp120”, Umashankara. M,  Karyn McFadden,  Isaac Zentner,  Arne Schön, Srivats Rajagopal,  Ferit Tuzer,  Syna A Kuriakose,  Mark Contarino, Judith LaLonde, Ernesto Freire,  and Irwin Chaiken, ChemMedChem n/a. doi: 10.1002/cmdc.201000222

Small-Molecule CD4 Mimics Interact with a Highly Conserved Pocket on HIV-1 gp120”, Navid Madani, Arne Schon, Amy M. Princiotto, Judith M. LaLonde, Joel R. Courter, Takahiro Soeta, Danny Ng, Liping Wang, Evan T. Brower, Shi-Hua Xiang, Young Do Kwon, Chih-chin Huang, Richard Wyatt, Peter D. Kwong, Ernesto Freire, Amos B. Smith III and Joseph Sodroski, Structure, 2008, 16, 1689-1701.

"Structure Based Development of Phenyl-imidazole-derived Inhibitors of  Indoleamine 2,3-Dioxygenase”, Sanjeev Kumar, Daniel Jaller, Bhumika Patel, Judith M. LaLonde, James B. DuHadaway, William P. Malachowski, George C. Prendergast and Alexander J. Muller .J. Med. Chem. 2008; 51, 4968–4977.

"Molecular determinants of click chemistry derived affinity enhancement of a dual antagonist peptide entry inhibitor of HIV-1 envelope gp120”, Hosahudya Gopi, Navid Madani, Vanessa Pirrone, Ferit Tuzer, Sabine Baxter, Judith LaLonde, Simon Cocklin, Fred C. Krebs, Joseph Sodroski and Irwin. M. Chaiken , J. Med. Chem. 2008, 51, 2638-2647.

“Targeting indoleamine 2,3-dioxygenase in cancer through development of potent naphthoquinone-based inhibitors”, Sanjeev Kumar, William P. Malachowski, James B. DuHadaway, Judith M. LaLonde, Patrick J. Carroll, Daniel Jaller, Richard Metz, George C. Prendergast and Alexander J. Muller, J. Med. Chem. 2008; 51(6); 1706-1718.

“Validation Studies of the Site-directed Docking Program LibDock”, Shashidhar N. Rao, Martha S. Head, Amit Kulkarni and Judith M. LaLonde, J.Chem. Info. Modeling 2007, 47, 2159-2171.

“A Critical Assessment of Docking Programs and Scoring Functions”, Warren, G.  L.; Andrews. C.W;  Capelli, A.-M; Clarke, B.; LaLonde, J.;  Lambert, M.H.; Lindvall, M.; Nevins,N.; Semus, S.F.; Senger, S.; Tedesco, G.; Wall, I. D.; Woolven, J. M. ; Peishoff, C. E. ;  Head, M.S; J. Med. Chem. 2006, 49 5912-31.