Molecular BiophysicsMolecular Biophysics

Fall 2008Fall 2008

Faculty and ResearchFaculty and Research

Brooklyn CollegeBrooklyn CollegeProf. Lesley Davenport Prof. Lesley Davenport -- SpectroscopySpectroscopyProf. Richard Prof. Richard Magliozzo Magliozzo -- EPR and Optical Spectroscopy, EPR and Optical Spectroscopy, EnzymologyEnzymology

City CollegeCity CollegeProf. Marco Prof. Marco Ceruso Ceruso -- Theoretical and Computational BiologyTheoretical and Computational BiologyProf. Prof. Sacha Sacha De Carlo De Carlo -- Structural Biology, Structural Biology, CryoCryo--electron electron MicroscopyMicroscopyProf. Prof. Ranajeet Ghose Ranajeet Ghose -- Structural Biology, Solution NMR, XStructural Biology, Solution NMR, X--Ray CrystallographyRay CrystallographyProf. Marilyn Gunner Prof. Marilyn Gunner -- Spectroscopy, Computational BiologySpectroscopy, Computational BiologyProf. Ronald Prof. Ronald Koder Koder -- Computational Protein Design, Solution and SolidComputational Protein Design, Solution and Solid--state NMRstate NMRProf. Kevin Ryan Prof. Kevin Ryan -- Chemical BiologyChemical BiologyDistinguished Prof. Ruth Stark Distinguished Prof. Ruth Stark -- Structural Biology, Solution and SolidStructural Biology, Solution and Solid--state NMRstate NMR

Hunter CollegeHunter CollegeProf. Dixie Goss Prof. Dixie Goss -- Fluorescence SpectroscopyFluorescence SpectroscopyProf. Nancy Prof. Nancy Greenbaum Greenbaum -- Structural Biology, Solution NMRStructural Biology, Solution NMRProf. Prof. Yujia Xu Yujia Xu -- Structural Biology, Solution NMR, Light Scattering TechniquesStructural Biology, Solution NMR, Light Scattering Techniques

College of Staten IslandCollege of Staten IslandDistinguished Prof. Fred Distinguished Prof. Fred Naider Naider -- Structural Biology, Solution and SolidStructural Biology, Solution and Solid--state NMRstate NMRProf. Prof. Sebastien Poget Sebastien Poget -- Structural Biology, Solution NMR (February 2009)Structural Biology, Solution NMR (February 2009)

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

Marco Ceruso (Assistant Professor, City Marco Ceruso (Assistant Professor, City College)College)

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

Computational Approaches to StudyComputational Approaches to StudyMechanisms of ReceptorMechanisms of Receptor--Mediated Signal Transmission Mediated Signal Transmission

across Membranesacross MembranesOur objectives areTo 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 classesEpidermal Growth Factor Receptors (involved in cellular motility, adhesion, apoptosis…) Ionotropic Glutamate Receptors(involved higher-order processes including memory and learning).

Coarse-Grained ModelsBecause 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.

SachaSacha De Carlo (Assistant Professor, City De Carlo (Assistant Professor, City College)College)

Cryo-Microscopy of Molecular MachinesOur 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 biological assemblies.

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

Molecular Basis of Transcription Initiation/Elongation in ArchaeaRecent 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 archaealRNA polymerase.

Two-component signal transduction in BacteriaAtomic 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 s54-dependent 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.

Electron Electron CryoCryo--microscopy of Molecular Machines and microscopy of Molecular Machines and Signal Transduction in Prokaryotes and Signal Transduction in Prokaryotes and ArchaeaArchaea

Lesley Davenport (Professor, Brooklyn Lesley Davenport (Professor, Brooklyn College)College)

G-Quadruplexed DNAGuanine-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.

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

Conformation, Dynamics and Interactions of Complex Conformation, Dynamics and Interactions of Complex Biomolecules Biomolecules

F(

6MI) G-Tetrad

G-Tetrad

TTA

GG

GTT

AG

FGTT

AG

GG

TTA

GG

G

F(

6MI) G-Tetrad

G-Tetrad

Porphyrin

K+ QIA

Our Research Approach: • Design Fluorescently Labeled Model DNA Human

Telomeric Sequences• Optical Spectroscopic Methods, Including Fluorescence

and Circular Dichroism

Our Research Goals:• To Understand G-Quadruplexed DNA

Conformation and Folding Dynamics• To Understand the Interactions of Quadruplex

Interactive Agents (QIAs) with Quadruplexed DNA as Potential Chemotherapeutics

Structural Biology of Viral Polymerase FunctionSpatial 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.

Structural Biology of Signal Transduction Structural Biology of Signal Transduction

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

Structural Biology of Intracellular SignalingStructural and dynamic determinants of the regulation of prokaryotic and eukaryotic protein kinases.

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

Ranajeet Ranajeet Ghose (Assistant Professor, Ghose (Assistant Professor, CCNY)CCNY)

Nancy Greenbaum (Professor, Hunter Nancy Greenbaum (Professor, Hunter College)College)

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

Structural Biology of preStructural Biology of pre--mRNA SplicingmRNA Splicing

*

*

5′ 3′

*

*

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

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

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

Cy3- * *

Cy5-

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

H+

e- H+

Put

in

light

GetOutATP

Light drives electron transfer drives proton transfer.A proton gradient is built up across a cell membrane.Charged electrons and proteins move through protein.

Make positive

Make negative

Computational and Spectroscopic Studies of PhotosynthesComputational and Spectroscopic Studies of PhotosynthesMarilyn Gunner (Professor, CCNY)Marilyn Gunner (Professor, CCNY)

Extract function of

interest

Design & synthesize Maquette

Learn and Apply

Respiratory/photosyntheticbc1 complex

Computational Protein Design to Understand Complicated Computational Protein Design to Understand Complicated Biochemical Processes Biochemical Processes

http://www.sci.ccny.cuny.edu/physics/faculty/koder.htm

Ronald Koder (Assistant Professor, CCNY)

Richard Richard Magliozzo Magliozzo (Professor, Brooklyn College)(Professor, Brooklyn College)

Mutations in catalase-peroxidase (KatG) cause drug resistant

tuberculosis infection

Wild-type KatG KatG[Ser315Thr] mutantTechniques we use to study enzymesSpectroscopyElectron paramagnetic resonance (EPR)Optical spectroscopyResonance Raman spectroscopyStopped-flow spectrophotometryRapid freeze-quench EPRIsothermal titration calorimetryMutagenesisX-ray crystallography

Kinetics

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

Study of the Origins of Resistance to the Antibiotic Study of the Origins of Resistance to the Antibiotic IsoniazidIsoniazid in in M. tuberculosisM. tuberculosis

MATαSte3p

Ste2p

MATa

WHWLQLKPGQPMY

Ste6p

YIIKGVFWDPAC-OCH3

aa--factorfactor

αα--factorfactor

SS

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

Structural Biology of GStructural Biology of G--Protein Coupled ReceptorsProtein Coupled ReceptorsFred Fred Naider Naider (Distinguished Professor, C.S.I.)(Distinguished Professor, C.S.I.)

How do olfactory GPCRs bind and discriminate small-molecule odorants?We design and synthesize probes to answer this question.

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

Molecular Recog.Molecular DesignOrganic synthesisBiological Assay

Learn:

The Nose: A Sensitive Chemical Detector……Using hundreds of

(G-Protein Coupled) Receptors (GPCRs)

Olefactory Olefactory Molecular RecognitionMolecular RecognitionKevin Ryan (Assistant Professor, CCNY)Kevin Ryan (Assistant Professor, CCNY)

Molecular Biophysics of Plant DefenseMolecular structure and biomechanics of plant cuticularmembranes and wound-healing biopolymers

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

Structural Biology of Fatty Acid SignallingMolecular recognition of fatty acid-binding proteins by ligands and peroxisome proliferator-activated receptors

13C Chemical Shift (ppm)

POLYSACCHARIDECAPSULE

CELL WALL

CYTOPLASM

CROSS-SECTION OF C. NEOFORMANS CELL

MELANIN LAYERIN CELL WALL

ANATOMY OF MELANIZED CELL

(A) (B)

N

C

I

II

AB

CD

E

F

G

H

I

J

Structural Biology of Membrane ProteinsSolid-state NMR of transmembrane domains of a G protein-coupled receptor

��� � ��GDP GTP

Molecular Structure of Fungal MelaninsSolid-state NMR approaches to melanin structure and biosynthesis

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

Molecular Interactions of Collagen Triple Helix: Folding, SelfMolecular Interactions of Collagen Triple Helix: Folding, Self--Assembly and Binding of ReceptorsAssembly and Binding of Receptors

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

We use biophysical approaches including NMR, MassWe use biophysical approaches including NMR, Mass--spec, lightspec, light--scattering scattering combined with mutagenesis to investigate the mechanisms of moleccombined with mutagenesis to investigate the mechanisms of molecular ular recognition of collagen triple helixrecognition of collagen triple helix

Yujia Yujia Xu (Assistant Professor, Hunter Xu (Assistant Professor, Hunter College)College)

New York Structural Biology CenterNew York Structural Biology Center

Situated at 133rd street and Convent Avenue on the City College campus.

All CUNY faculty have access to the facilities.

NMR500 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 CrystallographyThe NYSBC maintains the X4A (4-20 KeV) beamline at Brookhaven National Laboratories

Cryo-electron Microscopy and Tomography120 KV (1), 200 KV (2), 300 KV

Institute for Macromolecular Assemblies Institute for Macromolecular Assemblies (MMA)(MMA)

CUNY wide institute since 2003Associated faculty are based in all the senior collegesSupported by grants NYSTAR, CUNY’s Office of Academic Affairs,

Ge*NY*sisResearch efforts of individual faculty are funded through NSF and NIHDirected by Distinguished Prof. Ruth Stark

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.

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 equivalentMolecular Biophysics (U87901)Molecular Biophysics Seminar (U80541)

An undergraduate Biochemistry course may also be required in some cases.

Course RequirementsCourse Requirements

First Semester: U76000, U71000, U75000, U79041 & U80541Second Semester: BICM 77000, U79042, 2 electives & U80541Third Semester: U87901 & U80541Fourth Semester: U80541

The executive officer may allow additional credits of thesis research (U79500) after consultation with the program chairs.

Typical Course ScheduleTypical Course Schedule

22ndnd Level ExaminationLevel 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 InformationContact Information

Sub-discipline ChairsDistinguished Prof. Ruth Stark (stark@sci.ccny.cuny.edu)Prof. Ranajeet Ghose (ghose@sci.ccny.cuny.edu)