Molecular Biophysics

Fall 2008

Faculty and Research Choice of mentor and thesis committee usually after the 2nd semester

Brooklyn College Prof. Lesley Davenport - Spectroscopy Prof. Richard Magliozzo - EPR and Optical Spectroscopy, Enzymology

City College Prof. Marco Ceruso - Theoretical and Computational Biology Prof. Sacha De Carlo - Structural Biology, Cryo-electron Microscopy Prof. Ranajeet Ghose - Structural Biology, Solution NMR, X-Ray Crystallography Prof. Marilyn Gunner - Spectroscopy, Computational Biology Prof. Ronald Koder - Computational Protein Design, Solution and Solid-state NMR Prof. Kevin Ryan - Chemical Biology Distinguished Prof. Ruth Stark - Structural Biology, Solution and Solid-state NMR

Hunter College Prof. Dixie Goss - Fluorescence Spectroscopy Prof. Nancy Greenbaum - Structural Biology, Solution NMR Prof. Yujia Xu - Structural Biology, Solution NMR, Light Scattering Techniques

College of Staten Island Distinguished Prof. Fred Naider - Structural Biology, Solution and Solid-state NMR Prof. Sebastien Poget - Structural Biology, Solution NMR (February 2009)

Marco Ceruso (Assistant Professor, City ComputationalCollege) Approaches to Study Mechanisms of Receptor-Mediated Signal Transmission across Membranes Our objectives are To identify structural contexts for the various functional states of transmembrane signaling receptors. To characterize the energy landscapes and the molecular mechanisms underlying the transitions between these functional states.

Currently we focus on two distinct receptor classes Epidermal Growth Factor Receptors (involved in cellular motility, adhesion, apoptosis…) Ionotropic Glutamate Receptors (involved higher-order processes including memory and learning).

Coarse-Grained Models Because of the size and time-scale of the events that we study, we need to develop new tools for modeling and simulating accurately very large macromolecular assemblies in realistic environments.

http://www.sci.ccny.cuny.edu/~mcerus o

Sacha De Carlo (Assistant Professor, City College) Electron Cryo-microscopy of Molecular Machines and

Electron Cryo-microscopy of Molecular Machines and Signal Transduction in Prokaryotes and Archaea

Cryo-Microscopy of Molecular Machines Our research is focused on 3D electron microscopy and computer image processing to study the structure, function and dynamics of molecular assemblies involved in fundamental biological processes such as transcription. Cryo-EM has fostered substantial progress in studies of large Two-component biological assemblies. signal

transduction in Bacteria Atomic model of the bacterial enhancer-binding protein NtrC, built by docking high-resolution structures into low-resolution density maps derived from small- and wide-angle X-ray scattering (SAXS/WAXS) and electron microscopy (EM) data, shows the ring form of this s54dependent AAA+ ATPase. Understanding the molecular details will provide the mechanism by which these AAA+ ATPases perform mechanical work to remodel the s54-polymerase-DNA complex.

Molecular Basis of Transcription Initiation/Elongation in Archaea Recent work has focused on elucidating transcription initiation, elongation and regulatory mechanisms in Archaea. Our results directly map the position of the initiation ‘core’ complex (TBP/TFB transcription factors) onto the archaeal RNA polymerase.

http://www.planetesacha.com/Work.htm

Lesley Davenport (Professor, Brooklyn College) Conformation, Dynamics and Interactions of Complex Biomolecules G-Quadruplexed DNA

K+

QIA

Our Research Goals:

G-Tetrad F(6MI)

F(6MI)

TTAGGGTTAG FGTTAGGGTTAGGG

Guanine-rich sequences located at the end of chromosomes can assume highly stable G-Quadruplex structures, which inhibit the activity of telomerase, an enzyme that is important for tumorigenesis.

G-Tetrad

• Porphyrin

G-Tetrad

G-Tetrad

•

To Understand G-Quadruplexed DNA Conformation and Folding Dynamics To Understand the Interactions of Quadruplex Interactive Agents (QIAs) with Quadruplexed DNA as Potential Chemotherapeutics

Our Research Approach: • •

Design Fluorescently Labeled Model DNA Human Telomeric Sequences Optical Spectroscopic Methods, Including Fluorescence and Circular Dichroism

http://academic.brooklyn.cuny.edu/chem/davenport/

Ranajeet Ghose (Assistant Professor, CCNY) Structural Biology of Signal Transduction Structural Biology of Intracellular Signaling Structural and dynamic determinants of the regulation of prokaryotic and eukaryotic protein kinases.

Structural Biology of Viral Polymerase Function Spatial and temporal interactions between the components of the cystoviral polymerase complex and a functional model for the pathogenic rotaviruses using NMR and X-Ray crystallography.

Design of Novel Methodology to Quantify Protein Dynamics on Multiple Timescales Design and implementation of novel pulse sequences to study macromolecular structure and dynamics

http://www.sci.ccny.cuny.edu/~ghose

Nancy Greenbaum (Professor, Hunter College) Structural Biology of pre-mRNA Splicing Cy 5-

RNA structure and RNA-protein interactions Solution NMR and other spectroscopic techniques to identify understand molecular basis for spliceosome assembly and function.

*

Cy3-

*

RNA folding Time-resolved fluorescence techniques to determine the role of metal ions and spliceosomal proteins in folding of small nuclear (sn)RNAs into catalytically active conformations. * 5′

3′ *

* *

RNA-metal ion interactions Development of novel spectroscopic techniques to characterize essential metal ion binding sites.

http://www.hunter.cuny.edu/chem/greenbaum.shtml

Marilyn Gunner (Professor, CCNY) Computational and Spectroscopic Studies of Photosynthes Light drives electron transfer drives proton transfer. A proton gradient is built up across a cell membrane. Charged electrons and proteins move through protein.

e-

Make negative

Put

H+

Get Out ATP

in light

H+ Make positive http://www.sci.ccny.cuny.edu/~gunner

Ronald Koder (Assistant Professor, CCNY) Computational Protein Design to Understand Complicated Biochemical Processes

Extract function of interest

Design & synthesize Maquette

Learn and Apply Respiratory/photosynthetic bc1 complex http://www.sci.ccny.cuny.edu/physics/faculty/koder.ht m

Richard Magliozzo (Professor, Brooklyn College) Study of the Origins of Resistance to the Antibiotic Isoniazid in M. tuberculosis

Mutations in catalase-peroxidase (KatG) cause drug resistant tuberculosis infection

Wild-type KatG

KatG[Ser315Thr] mutant

Techniques we use to study enzymes Spectroscopy Electron paramagnetic resonance (EPR) Optical spectroscopy Resonance Raman spectroscopy Stopped-flow spectrophotometry Rapid freeze-quench EPR Kinetics Isothermal titration calorimetry Mutagenesis X-ray crystallography

academic.brooklyn.cuny.edu/chem/magliozzo/index.htm

Fred Naider (Distinguished Professor, C.S.I.) Structural Biology of G-Protein Coupled Receptors WHWLQLKPGQPMY

α-factor MATα Ste3p

Ste2p

MATa a-factor

Ste6p

YIIKGVFWDPAC-OCH3

S

We use mating in yeast as a paradigm to analyze the biophysics of G protein coupled receptors. Our group uses CD, NMR and Fluorescence approaches. A-Yeast mating. B-GPCR (Ste2p) initiated signal transduction pathway. C-Kay labeling to assign methyl protons in 13C-HSQC. D-NMR structure for TM1-TM2 region of Ste2p.

www.chem.csi.cuny.edu/naider/naider.htm

Kevin Ryan (Assistant Professor, CCNY) Olefactory Molecular Recognition How do olfactory GPCRs bind and discriminate small-molecule odorants? We design and synthesize probes to answer this question. The Nose: A Sensitive Chemical Detector… …Using hundreds of (G-Protein Coupled) Receptors (GPCRs)

Learn: Molecular Recog. Molecular Design Organic synthesis Biological Assay

http://www.sci.ccny.cuny.edu/~kr107/index2/index.html

Ruth Stark (Distinguished Professor,CCNY) Structural Biology of Macromolecular Assemblies Structural Signalling

Biology

of

Fatty

Acid

Molecular recognition of fatty acid-binding proteins by ligands and peroxisome proliferator-activated (A) (B) II receptors I

Molecular Biophysics of Plant Defense

J I E D

H C G B

C

Molecular structure and biomechanics of plant cuticular membranes and wound-healing biopolymers

A

F N

Molecular Melanins

ANATOMY OF MELANIZED CELL

Structure

of

Fungal

MELANIN LAYER IN CELL WALL

Solid-state NMR approaches to melanin structure POLYSACCHARIDE and biosynthesis CAPSULE CELL WALL

CYTOPLASM

GDP

Structural Proteins

Biology

GTP

of

Membrane

Solid-state NMR of transmembrane domains of a G protein-coupled receptor 13

C Chemical Shift (ppm)

CROSS-SECTION OF C. NEOFORMANS CELL

http://www.sci.ccny.cuny.edu/resgroup

Yujia Xu (Assistant Professor, Hunter College) Molecular Interactions of Collagen Triple Helix: Folding, SelfAssembly and Binding of Receptors

We use biophysical approaches including NMR, Mass-spec, light-scattering combined with mutagenesis to investigate the mechanisms of molecular recognition of collagen triple helix http://www.hunter.cuny.edu/chem/xu.shtml

New York Structural Biology Center ‰Situated at 133rd street and Convent Avenue on the City College campus. ‰All CUNY faculty have access to the facilities. NMR 500 MHz (1), 600 MHz (1), 700 MHz (1), 750 MHz (1), 800 MHz(3), 900 MHz (2) All spectrometers have latest generation cryogenic probes. X-Ray Crystallography The NYSBC maintains the X4A (4-20 KeV) beamline at Brookhaven National Laboratories Cryo-electron Microscopy and Tomography 120 KV (1), 200 KV (2), 300 KV

Institute for Macromolecular Assemblies (MMA)

Research in the institute is positioned at the interface of biology, chemistry, physics and engineering and devoted to the study of naturally occurring macromolecular machines and the design and fabrication of artificial ones. ‰ CUNY wide institute since 2003 ‰ Associated faculty are based in all the senior colleges ‰ Supported by grants NYSTAR, CUNY’s Office of Academic Affairs, Ge*NY*sis ‰ Research efforts of individual faculty are funded through NSF and NIH ‰ Directed by Distinguished Prof. Ruth Stark

Course Requirements

The following courses (or exemptions) are required: Advanced Inorganic Chemistry (U71000) Advanced Organic Chemistry I (U75000) Introductory Quantum Chemistry (U76000) Basic Laboratory Techniques for Molecular Biophysics I (U79041) Basic Laboratory Techniques for Molecular Biophysics II (U79042)

The following courses are required: Physical Biochemistry (BICM 77000) or other graduate equivalent Molecular Biophysics (U87901) Molecular Biophysics Seminar (U80541) An undergraduate Biochemistry course may also be required in some cases.

Typical Course Schedule First Semester: U76000, U71000, U75000, U79041 & U80541 Second Semester: BICM 77000, U79042, 2 electives & U80541 Third Semester: U87901 & U80541 Fourth Semester: U80541 The executive officer may allow additional credits of thesis research (U79500) after consultation with the program chairs.

2nd Level Examination ‰The second-level examination consists of U87901 and a related original research proposal. ‰The proposal should be in an area outside that of the student's dissertation research. ‰Should be defended orally before or during the fourth semester of study. ‰Grading scale includes High Pass (A), Pass (B), Conditional Pass (C), and Fail. ‰The average of the grades on the oral defense and U87901 must be no lower than B, and neither grade may be lower than C. ‰Students who enter the program with advanced course standing must follow an earlier schedule, as determined by the sub-discipline chairs.

Contact Information Sub-discipline Chairs Distinguished Prof. Ruth Stark ([email protected]) Prof. Ranajeet Ghose ([email protected])