Roger Armen

Postdoctoral Associate

My broad research interests are in the molecular basis of human disease including cancer, viral infections, and amyloid disease. The central focus of my research is the molecular detail of specific protein-ligand and protein-protein interactions. Molecular docking and dynamics studies can elucidate molecular details of the dynamics of a protein target and predict the most reasonable binding modes for ligands with no structural data. These computational methods can be used to augment medicinal chemistry efforts to design derivatives of lead compounds, identify putative new ligand classes (chemotypes), and compare the binding of a given ligand to the target protein and to other related off-target proteins.

Karunesh Arora

Multiscale modeling of Biomacromolecules

Website: http://sitemaker.umich.edu/karunesh

I am interested in the application of the state-of-the-art computer simulation methods (e.g., path sampling, string methods, umbrella sampling etc.) to obtain quantitative insights into the complex biological processes that occur over a range of spatial and temporal scales. Over the past several years I have successfully applied theory and computational methods to gain quantitative insights into the regulatory and long-time processes in DNA and proteins, specifically protein-ligand and protein-nucleic acid interactions involved in DNA replication and repair, allosteric transitions in kinases and chaperone proteins, and mechanochemical coupling in the helicase motor protein.

Selected publications:

K. Arora and C. L. Brooks III, “Large-scale allosteric conformational transitions of Adenylate kinase appear to involve population-shift mechanism” 2007, Proc. Natl. Acad. Sci, USA, 104, 18496.

K. Arora and C. L. Brooks III, "Functionally important conformations of Met20 loop in dihydrofolate reductase are populated by rapid thermal fluctuations", J. Amer. Chem. Soc., 2009, 131, 5642.

K. Arora, W. A. Beard, S. H. Wilson and T. Schlick, "Mismatch-induced conformational distortions in pol beta/DNA complex support an induced-fit mechanism for fidelity", 2005, Biochemistry, 44, 13328.

K. Arora and T. Schlick, "The conformational transition pathway by the stochastic path algorithm of polymerase beta/DNA upon binding correct incoming substrate", 2005, J. Phys. Chem. B, 109, 5358.

Francesca Bardinelli

Undergraduate Research Student

I'm a Junior Chemistry major currently working on free energy methods, and exploring the interactions of small molecule inhibitors of the enzyme dihydrofolate reductase.

David Bostick

Postdoctoral Associate

David Bostick's Homepage

David Braun

Manager of Computational Facilities

Phone: 734 615 1450

Since 1996 David has been configuring, installing, and managing high performance computing and data centers.

Charles Brooks

Professor

Website: http://brooks.chem.lsa.umich.edu

Alana Canfield

Graduate Student

Jun Feng

Postdoctoral Fellow

Phone: 734-615-2971

Gene activity can be regulated at the transcriptional level through riboswitch, in which transcription of mRNA is controlled by sensing the related metabolite concentration. I am currently interested in the study of preQ1 riboswitch, the smallest riboswitch ever known.
By computational means, we seek to depict the molecular detail of the aptamer conformational transitions upon ligand binding.

Jessica Gagnon

Chemistry Grad Student - Rotating in Brooks Group

I'm a new graduate student in the department of Chemistry. I am carrying out a rotation project in Dr Brooks' group focusing on protein-ligand docking.

Mike Garrahan

Programmer

Contact Mike Garrahan

Currently working on CHARMM code modernization. Joined the Brooks Group in 2009 after 12 years in commercial software development. Interests include software engineering, physical simulation, signal processing, astronomy, and classical music.

Surendra Jain

Postdoctoral Associate

Computational study of the translocation mechanism in the Maltose ABC transporter

ATP-Binding Cassette (ABC) transporters are a class of small molecular machines that utilize the energy from the hydrolysis of ATP to translocate a wide variety of substrates across cells. These ABC transporters are basically made up of four protein domains or subunits: two hydrophobic membrane spanning domains (MSDs) that are believed to form the translocation pathway across the membrane and two hydrophilic nucleotide binding domains (NBDs) that interact with the cytoplasmic surface. The NBDs bind ATP and provide energy for the active transport of the substrate. Apart from the four subunits, some ABC transporters also require a substrate binding protein (SBP) for their function. These SBPs selectively bind substrates and interact with the MSDs to translocate the substrate across membranes. The crystal structures of many ABC transporters have been solved.

One such ABC transporter is the Maltose transporter which translocates maltose from the periplasm side of the cell to the cytoplasm. It consists of two membrane spanning domains and two nucleotide binding domains. The two nucleotide binding domains form a homo dimer. In addition, the maltose transporter requires a maltose binding protein (MBP) for its function. Three crystal structures of the maltose NBDs are available: (1) Open form of the NBD when it is not bound to ATP (2) Semi Open form and (3) closed from of the NBD with ATP bound. There are also crystal structures available for the open (maltose free) and closed (maltose bound) form of the MBPs. Recently, a crystal structure of the full Maltose transporter with the maltose and ATP bound has been reported (see figure 1). However, a detailed mechanistic understanding of the translocation process in these ABC transporters is still not clear. In this project, we use Normal mode analysis along with atomistic molecular dynamics simulations to understand the translocation mechanism in the Maltose ABC transporter.

Anastasia Kennedy

Administrative Assistant JCC Editorial Assistant

Phone: 734-763-2353

Jennifer Knight

Development of free energy simulation methods

Website: http://www.umich.edu/~jeknight

Phone: 732-648-7297

I am working to develop free energy methods for structure-based drug design. My research interests involve developing computational methods for optimizing small molecule therapeutics and for exploring relationships between structure and biological function in macromolecules.

Alexander Leung

Website Developer

I am currently a Junior at the University of Michigan pursuing a Computer Engineering Degree. Working with the Brooks Group over summer 2009, redesigned this website from this:

To what it is currently.

testing

Now I've made some changes, did this work?

Ranjan Mannigie

Graduate Student

I'm a PhD candidate at the Scripps Research Institute's Kellogg School of Science and Technology (have been since fall 2004), and am interested in various aspects of protein science (especially design and understanding design criteria for assemblies). Broadly, I have been working on virus capsid design (by theory and electron microscopy), forcefield parameterization, coarse graining, protein design and 'exasperating my advisor'.

Eric May

NSF Postdoctoral Fellow

Website: http://sitemaker.umich.edu/ericmay/home

Ronald Mills

Undergraduate Research Student

I am an undergraduate working with Jennifer Knight and Dr Brooks on structural transitions between the inactive and active states of GPCRs, and bovine rhodopsin specifically.

Rohit Singh

Biophysics rotation student

I am rotating in the Brooks group and working on Abeta oligomer formation as a function of pH.

Joe Yesselman

Graduate student in Biophysics

I am working under the co-mentorship of Drs Brooks and Al-Hashimi in Biophysics. My project is focused on ligand design and docking to flexible RNA targets.""