- compbio-allhands@cgl.ucsf.edu - RBVI Mailing Lists

[Compbio-allhands] PETER A. KOLLMAN LECTURESHIP - April 3, 2014
by Flowers, Nicole 01 Apr '14

01 Apr '14

THURSDAY, APRIL 3, 2014 AT 12:00 PM PETER A. KOLLMAN LECTURESHIP GENENTECH HALL BYERS AUDITORIUM - UCSF MISSION BAY CAMPUS SIMULCAST TO PARNASSUS CAMPUS LIBRARY 221 WEBCAST: Reception in Byers Hall 5th Floor Lounge at 3:30 Please see attached flyer. Nicole Takesono Flowers CCB Graduate Program Assistant AMBER Software Administrator UCSF MC 2280 600 16th St. Genentech Hall Room 522 San Francisco, CA 94158-2517 Phone: (415) 502-6518 Fax: (415) 514-1546

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[Compbio-allhands] Fwd: Job offers at CRG-CNAG
by Tom Ferrin 17 Mar '14

17 Mar '14

-------- Original Message -------- Subject: Job offers at CRG-CNAG Date: Mon, 17 Mar 2014 15:32:34 +0100 From: Marc A. Marti-Renom <mmarti(a)pcb.ub.cat> To: Marc A. Marti-Renom <mmarti(a)pcb.ub.cat> Dear friends and colleagues (apologies for the mass posting), I would appreciate if you pass this e-mail to whom may be interested on working in 4D (structure and dynamics) genomics at the CRG and CNAG in Barcelona. Together with the Beato, Graf and Filion Labs, we have recently opened several positions to work on experimental and computational aspects of our ERC Synergy grant "/4DGenome: Dynamics of human genome architecture in stable and transient gene expression changes/". More details here for the four levels of expertise we seek: Postdocs http://www.nature.com/naturejobs/science/jobs/391399-for-postdoc-position Bioinformaticians http://www.nature.com/naturejobs/science/jobs/391401-for-bioinformatician-p… Technicianshttp://www.nature.com/naturejobs/science/jobs/391403-for-technic… PhDshttp://www.nature.com/naturejobs/science/jobs/391405-for-phd-position Many thanks in advance, Marc ... *Marc A. Marti-Renom, ICREA Research Professor* *Genome Biology Group Leader - CNAG - Centre Nacional d’Anàlisi Genòmica* *Structural Genomics Group Leader - CRG - Centre de Regulació Genòmica* Parc Científic de Barcelona – Torre I Baldiri Reixac, 4, 08028 Barcelona Tel +34 9340 33743 Email _mmarti(a)pcb.ub.cat <mailto:mmarti@pcb.ub.cat>_ Web _http://marciuslab.org_ - _http://cnag.cat_ - _http://crg.cat_ *** Consider the environment. Print responsibly. ***

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[Compbio-allhands] 3/13/14 Seminar with Tim Hughes
by Flowers, Nicole 07 Mar '14

07 Mar '14

BBC Graduate Programs Seminar Series Bioinformatics Biophysics Chemistry & Chemical Biology Complex Biological Sytems Thursdays, 12 Noon Genentech Hall Auditorium Simulcast to Parnassus Campus S-161 Tim Hughes University of Toronto Kaleidoscopic evolution of C2H2 zinc finger DNA Binding March 13, 2014 N. Krogan, Host BBC Seminars are supported by the Biophysics, Bioinformatics, and Chemistry & Chemical Biology IFM, Department of Pharmaceutical Chemistry, QBC, HARC Center, the Center for Systems and Synthetic Biology, and the Quantitative Student Group Series. Nicole Takesono Flowers CCB Graduate Program Assistant AMBER Software Administrator UCSF MC 2280 600 16th St. Genentech Hall Room 522 San Francisco, CA 94158-2517 Phone: (415) 502-6518 Fax: (415) 514-1546

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[Compbio-allhands] Fwd: Scientist - Molecular modeller/simulator position at Novozymes
by Jacobson, Matt 06 Mar '14

06 Mar '14

Begin forwarded message: From: "Wittmann, Torsten" <Torsten.Wittmann(a)ucsf.edu<mailto:Torsten.Wittmann@ucsf.edu>> Subject: Fwd: Scientist - Molecular modeller/simulator position at Novozymes Date: March 6, 2014 10:05:51 AM PST To: "Jacobson, Matt" <Matt.Jacobson(a)ucsf.edu<mailto:Matt.Jacobson@ucsf.edu>> In case you have anyone looking for jobs. Sent from my iPhone Begin forwarded message: From: "JEIN (Jens Erik Nielsen)" <JEIN(a)novozymes.com<mailto:JEIN@novozymes.com>> Date: March 6, 2014, 12:27:26 AM PST To: "JEIN (Jens Erik Nielsen)" <JEIN(a)novozymes.com<mailto:JEIN@novozymes.com>> Subject: Scientist - Molecular modeller/simulator position at Novozymes Dear All Please see the job ad below. We are looking for a talented person with a molecular modelling/simulation background who will have a big impact on the protein engineering projects that will develop new products for the world’s largest producer of industrial enzymes. http://novozymes.com/en/careers/jobs/Pages/52705.aspx Best wishes Jens ------------------------------------- Jens Erik Nielsen Senior Manager Novozymes A/S Krogshoejvej 36 2880 Bagsvaerd Denmark Phone: +45 44461692 Mobile: +45 30771692 E-mail: jein(a)novozymes.com<mailto:jein@novozymes.com> Web: www.novozymes.com<http://www.novozymes.com/> Follow Novozymes on: LinkedIn<http://www.linkedin.com/company/novozymes/> | Twitter<https://twitter.com/Novozymes/> Novozymes A/S (reg. no.:10007127). Registered address: Krogshoejvej 36 DK-2880 Bagsvaerd, Denmark This e-mail (including any attachments) is for the intended addressee(s) only and may contain confidential and/or proprietary information protected by law. You are hereby notified that any unauthorized reading, disclosure, copying or distribution of this e-mail or use of information herein is strictly prohibited. If you are not an intended recipient you should delete this e-mail immediately. Thank you. Matthew P. Jacobson Professor, Department of Pharmaceutical Chemistry Department of Bioengineering and Therapeutic Sciences California Institute for Quantitative Biosciences Institute for Neurodegenerative Diseases Director, Graduate Group in Biophysics UCSF MC 2540 1700 4th St., Byers Hall, Room 408E San Francisco, CA 94158-2330 matt.jacobson(a)ucsf.edu<mailto:matt.jacobson@ucsf.edu> jacobsonlab.org<http://jacobsonlab.org>

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[Compbio-allhands] Seminar - Friedrich Foerster, Max Planck Institute, March 11, 2014 - 10am - GH S261
by Hilary Mahon 05 Mar '14

05 Mar '14

--- Hilary Mahon Assistant to Dr. Sali University of California, San Francisco MC 2552 Byers Hall Room 503 1700 4th Street San Francisco, CA 94158-2330 Phone +1 (415) 514 4228 Fax +1 (415) 514 4231 Email hilary(a)salilab.org

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[Compbio-allhands] Fwd: Job Postings for Life Scientists
by Jacobson, Matt 04 Mar '14

04 Mar '14

Begin forwarded message: From: "Lindstaedt, Bill" <Bill.Lindstaedt(a)UCSF.EDU<mailto:Bill.Lindstaedt@UCSF.EDU>> Subject: Job Postings for Life Scientists Date: March 4, 2014 9:52:56 AM PST To: <BPSTUDENTS(a)LISTSRV.UCSF.EDU<mailto:BPSTUDENTS@LISTSRV.UCSF.EDU>> Reply-To: "Lindstaedt, Bill" <Bill.Lindstaedt(a)UCSF.EDU<mailto:Bill.Lindstaedt@UCSF.EDU>> Bio-rad (note: 2 separate positions) (1) Sr. R&D Engineer, Microfluidics department Pleasanton, California Job Description<https://biorad-openhire.silkroad.com/epostings/index.cfm?fuseaction=app.job…> The R&D engineer will design and build new instruments, and develop control and analytical software. You will develop mechatronics and optical systems as well as microfluidic devices. You will have the opportunity to develop these instruments from the research stage through product development. Required Skills • Hands-on working knowledge of microfluidics and automated fluidics instrumentation • Detailed understanding of laminar and liquid-liquid fluid flows • Experience manipulating microliter volumes of fluid • Experience in MEMS and/ or microfluidics fabrication • Proficient with SolidWorks • Proficient in programming in Python, MATLAB or C++ • Capable of developing and executing experimental protocols, and communicating findings clearly and concisely Required Experience • Degree in Mechanical Engineering, Chemical Engineering, or equivalent field • PhD and industrial experience, or MS or BS degree with equivalent research experience --- (2) Staff Scientist, Microfluidics department Pleasanton, California Job Description<https://biorad-openhire.silkroad.com/epostings/index.cfm?fuseaction=app.job…> The staff scientist will help to lead the biology and biochemistry efforts in the group to develop the next generation of products. This is a multidisciplinary group and we will work on a multitude of systems from nucleic acids to proteins and cells. You will devise and develop assays and work intimately with the engineering group developing instrumentation. Finally, we are growing the Digital Biology Center to be the preeminent center for droplet microfluidics research. You will be a foundational member of the group and we look forward to your influence and creativity choosing future research directions. Required Skills • A proven track record of assay design, development and implementation. • Experience with NGS sample preparation methods • Familiarty with ELISA and other protein analysis methods • Experience developing and optimizing nucleic acids protocols, such as PCR. • Experience leading other scientists. • Excellence in written and oral communication. • PhD in biology, biochemistry, Chemical Engineering, or similar field • 3-5+ years experience in industry or academia post PhD or equivalent Apply online or contact Paul Korn paul_korn(a)bio-rad.com<mailto:paul_korn@bio-rad.com> at HR for questions. D. E. Shaw Research Postdoctoral Fellow New York, New York Job Description<https://careers.deshawresearch.com/recruit/JoiningDepartment.html>; or see attachment D. E. Shaw Research is seeking postdoctoral fellows of exceptional ability to join our New York-based team. This is a unique opportunity to develop and work with transformative technology in a dynamic, interdisciplinary environment. Candidates should have expertise in computational chemistry, biology, or physics, or in a relevant area of computer science or applied mathematics. Relevant areas of experience • the study of allosteric interactions or other functionally important conformational changes in biological molecules • structure prediction or design for proteins or RNA • the study of protein–protein or protein–nucleic acid interactions • force field improvement through detailed comparisons of simulation data with NMR measurements • development and implementation of new methodology (e.g., integrators, methods for enhanced sampling or free-energy calculations, or tools to efficiently analyze large simulation datasets). Application URL: http://www.deshawresearch.com/recruit/jobs/Oncampus/UCSF/PF Either apply online or send a CV or resume to Želimir Galjanić at Zelimir.Galjanic(a)career.DEShawResearch.com<mailto:Zelimir.Galjanic@career.DEShawResearch.com>. BioCentury Publications, Inc Senior Writer San Francisco, CA or Chicago, Illinois (See attachment) BioCentury Publications Inc. is widely known as the leading provider of business intelligence about the biotechnology and pharmaceutical industries through its high value-added newsletters, conferences and research services. The company currently has openings for Senior Writers to evaluate scientific developments, clinical research, regulatory and public policy developments for their healthcare, commercial and investment impact and write about them for our publications. Requirements • 4+ years work experience or other credentials to demonstrate advanced knowledge of the topics addressed by the company’s publications and services. • ability to write complex, multi-source articles of up to 3,000 words at least six times a year that identify emerging trends and engage in interpretative, forward-looking thinking. • expected to produce an average of at least two pages of published copy per week. • The ability to write clearly and accurately in English that is correct with respect to grammar, spelling and style, within the company’s deadlines. Fluency in a language other than English is highly desirable. • The ability to think analytically, to be able to evaluate the potential outcomes of actions or events, to communicate this reasoning in writing and, where appropriate, to provide supporting numerical analysis. Experience with financial modeling is highly desirable. • News judgment, i.e., the ability to prioritize news events in order of importance for the company’s audience, and to be able to explain the reasoning behind the ranking. Please contact Susan Morgan,smorgan(a)biocentury.com<mailto:smorgan@biocentury.com> Director of HR, BioCentury Publications, Inc. Bio-rad Scientist, BioEducation R&D Hercules, CA Job Description<https://biorad-openhire.silkroad.com/epostings/index.cfm?fuseaction=app.job…> Bio-Rad believes that the biotechnology industry should play an integral role in supporting education, helping to develop today's students as tomorrow's scientists and problem solvers. Bio-Rad's Biotechnology Explorer program (www.explorer.bio-rad.com<http://www.explorer.bio-rad.com/>) has developed a line of laboratory kits which have provided millions of students around the world the opportunity to explore the fundamental techniques of genetic engineering, DNA fingerprinting, DNA amplification, protein expression and analysis, bioinformatics, and the creation of genetically modified organisms. Required Skills • The primary job responsibility is to develop hands-on biotechnology educational kits and activities for use in teaching labs at the high school, community college and university levels. • Performing the necessary laboratory work required to develop and validate new kits, and managing the project through the new product development process. • Technically support all existing products and be an expert source for technical questions related to all of our products for both internal and external inquiries. • Have an understanding of the education market and US educational system and participate in marketing activities and is expected to interact frequently with teachers and students. • Attend and support training workshops for teachers. The job requires 10-15% time traveling to tradeshows and customer visits. Education: MS (with industry work experience) or PhD in a life science discipline. Engineering, Bioinformatics, chemistry or environmental science background is a plus. The ideal candidate will minimally have completed a life science-based doctoral graduate program or have equivalent work experience. Required Experience • Passion for science education and be excited to work as part of a dynamic, fast paced, and highly motivated team. • Have balanced laboratory skills including molecular biology, protein biochemistry, and bioinformatics analysis. • Broad knowledge base of biology and science in general • Computer programming experience is a plus • Some teaching experience; experience working with teachers to deliver new classroom content are preferred. • Product development experience in industry are highly desirable. Bryony Ruegg, PhD Business Unit Manager Biotechnology Explorer Program Bio-Rad Laboratories, Inc. Email: bryony_ruegg(a)bio-rad.com<mailto:bryony_ruegg@bio-rad.com> Nodality (note: 2 separate positions) Nodality is a start-up biotechnology company with a unique technology that reveals biological function to enable better drug development, diagnostics and patient care. We are seeking qualified applicants for the position of Scientist I/II, Research. The scope of research will address the application of flow cytometric analysis to the interrogation of immune cell signaling in the context of development of therapeutic drugs and diagnostic tests for autoimmune disorders, cancer immunotherapy and hematologic malignancies. (1) Scientist I/II, Research South San Francisco, CA (See attachment) Functions: • Apply and further develop Nodality's SCNP technology to address clinically relevant questions addressing both disease biology and drug development. • Work effectively in multidisciplinary teams including clinical and computational sciences, addressing diverse scientific and clinical questions. • Apply understanding/knowledge of signaling biology to develop SCNP assays for continued expansion of biological scope and disease-based applications. • Effectively operate within multiple projects with varied objectives and timelines. Education and Experience: • PhD in a relevant discipline (or equivalent experience if all other criteria are met);minimal 2 yrs industry experience • Understanding / knowledge of signaling biology is essential and experience in cancer immunotherapy is a plus. • Knowledge of principles of flow cytometry is essential, hands-on experience is highly desirable. • Immunological background is preferred. • Excellent verbal and written communication skills are essential. --- (2) Scientist, Bioinformatics/Data Scientist South San Francisco, CA (See attachment) Responsibilities: • Work with biologists to design experiments to answer complex biological and clinical questions in oncology, autoimmunity, and immunology • Perform a variety of data analysis tasks ranging from exploring biology to developing and validating predictive models for clinical applications • Work in cross-functional teams with research biologists, technology experts, biostatisticians, clinical scientists, and computational scientists • Use your programming skills to efficiently manage experimental data and data workflows • Contribute to development of study protocols, statistical analysis plans and reports • Explore, evaluate, and implement novel approaches and data analysis methods for interpreting biological experiments and improving processes • Present proposals and findings within and beyond your team Job Requirements: • A PhD with strong background in computational biology, biostatistics, bioinformatics, computer science, data science or related field • Knowledge of molecular and cellular biology and experience working with biological data • Knowledge of statistical and machine learning techniques • Proficiency with popular statistical packages such as R • Proficiency with Python • Understanding of database systems (SQL, MongoDB, etc.) • Knowledge of web development languages and packages such as JavaScript, D3.js is a plus Please submit your resume with cover letter to jobs(a)nodalityinc.com<mailto:jobs@nodalityinc.com>. Nodality is an equal opportunity employer. -- Thi Nguyen, PhD Program Director, Career Development Graduate Students and Postdocs Office of Career and Professional Development Student Academic Affairs University of California, San Francisco 1675 Owens St, Ste 310 San Francisco, CA 94143 Phone: 415-514-4750 career.ucsf.edu<http://career.ucsf.edu> Please schedule meetings through Celestine Fry: 415-476-4986, ocpd(a)ucsf.edu<mailto:ocpd@ucsf.edu> --- Bill Lindstaedt, MS Director Office of Career and Professional Development Student Academic Affairs University of California, San Francisco 513 Parnassus Ave., Room S-140 San Francisco, CA 94143 Phone: 415-502-2422 career.ucsf.edu<http://career.ucsf.edu> Please schedule meetings through Celestine Fry: 415-476-4986, ocpd(a)ucsf.edu<mailto:ocpd@ucsf.edu> ________________________________ Use this link to unsubscribe<http://listsrv.ucsf.edu/cgi-bin/wa?SUBED1=BPSTUDENTS&A=1> from this mailing list. Matthew P. Jacobson Professor, Department of Pharmaceutical Chemistry Department of Bioengineering and Therapeutic Sciences California Institute for Quantitative Biosciences Institute for Neurodegenerative Diseases Director, Graduate Group in Biophysics UCSF MC 2540 1700 4th St., Byers Hall, Room 408E San Francisco, CA 94158-2330 matt.jacobson(a)ucsf.edu<mailto:matt.jacobson@ucsf.edu> jacobsonlab.org<http://jacobsonlab.org>

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[Compbio-allhands] Fwd: Postdoc Positions Available
by Jacobson, Matt 26 Feb '14

26 Feb '14

Begin forwarded message: From: Sharon Hammes-Schiffer <shs3(a)illinois.edu<mailto:shs3@illinois.edu>> Subject: Postdoc Positions Available Date: February 26, 2014 4:17:02 PM PST To: undisclosed-recipients:; Dear Colleague, I would appreciate your help in forwarding this e-mail to potential postdoc candidates. Best regards, Sharon POSTDOCTORAL POSITIONS AVAILABLE Several postdoctoral positions are currently available in my group at the University of Illinois at Urbana-Champaign. I am particularly seeking candidates interested in working on biologically oriented projects. These projects are focused on understanding the fundamental principles underlying enzyme and ribozyme catalysis, especially the roles of electrostatics, hydrogen bonding, and protein motion. One of the current projects centers on the use of nitrile probes placed at specific sites within an enzyme to examine the electrostatic and conformational changes along the catalytic cycle via the vibrational frequency shifts. Another current project uses mixed quantum mechanical/molecular mechanical (QM/MM) free energy methods to elucidate the mechanisms of several different ribozymes. Other projects focus on proton-coupled electron transfer (PCET) in enzymes. Two relevant papers are listed below, and additional information can be found on my group web site: http://www.scs.illinois.edu/schiffer/. Interested candidates should send a CV to me at shs3(a)illinois.edu<mailto:shs3@illinois.edu>. J. Layfield and S. Hammes-Schiffer, "Calculation of vibrational shifts of nitrile probes in the active site of ketosteroid isomerase upon ligand binding," J. Am. Chem. Soc. 135, 717-725 (2013). A. Ganguly, P. Thaplyal, E. Rosta, P. C. Bevilacqua, and S. Hammes-Schiffer, "Quantum mechanical/molecular mechanical free energy simulations of the self-cleavage reaction in the hepatitis delta virus ribozyme," J. Am. Chem. Soc. 136, 1483-1496 (2014). -- Sharon Hammes-Schiffer Swanlund Professor of Chemistry Department of Chemistry University of Illinois at Urbana-Champaign A410 Chemical & Life Sciences Laboratory 600 South Mathews Avenue Urbana, IL 61801-3364 Phone: (217) 300-0335 Fax: (217) 244-3186 e-mail: shs3(a)illinois.edu<mailto:shs3@illinois.edu> http://www.scs.illinois.edu/schiffer/ Matthew P. Jacobson Professor, Department of Pharmaceutical Chemistry Department of Bioengineering and Therapeutic Sciences California Institute for Quantitative Biosciences Institute for Neurodegenerative Diseases Director, Graduate Group in Biophysics UCSF MC 2540 1700 4th St., Byers Hall, Room 408E San Francisco, CA 94158-2330 matt.jacobson(a)ucsf.edu<mailto:matt.jacobson@ucsf.edu> jacobsonlab.org<http://jacobsonlab.org>

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[Compbio-allhands] Stefan Boresch talk today
by Jacobson, Matt 25 Feb '14

25 Feb '14

Noon, BH212 Stefan Boresch, U. Vienna "Free energy simulations: from boring methodological work to a promising novel approach for QM/MM" http://www.mdy.univie.ac.at/en/people/boresch/boresch.html Matthew P. Jacobson Professor, Department of Pharmaceutical Chemistry Department of Bioengineering and Therapeutic Sciences California Institute for Quantitative Biosciences Institute for Neurodegenerative Diseases Director, Graduate Group in Biophysics UCSF MC 2540 1700 4th St., Byers Hall, Room 408E San Francisco, CA 94158-2330 matt.jacobson(a)ucsf.edu<mailto:matt.jacobson@ucsf.edu> jacobsonlab.org<http://jacobsonlab.org>

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[Compbio-allhands] 2/27/14 Seminar with Bianxiao Cui
by Nicole Takesono Flowers 21 Feb '14

21 Feb '14

BBC Graduate Programs Seminar Series Bioinformatics Biophysics Chemistry & Chemical Biology Complex Biological Sytems Thursdays, 12 Noon Genentech Hall Auditorium Simulcast to Parnassus Campus S-161 Bianxiao Cui Stanford Light-controlled intracellular signaling pathways in cell fate determination February 27, 2014 B. Huang, Host BBC Seminars are supported by the Biophysics, Bioinformatics, and Chemistry & Chemical Biology IFM, Department of Pharmaceutical Chemistry, QBC, HARC Center, the Center for Systems and Synthetic Biology, and the Quantitative Student Group Series. Nicole Takesono Flowers CCB Graduate Program Assistant AMBER Software Administrator UCSF MC 2280 600 16th St. Genentech Hall Room 522 San Francisco, CA 94158-2517 Phone: (415) 502-6518 Fax: (415) 514-1546

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[Compbio-allhands] Fwd: Cool Kinase Talk (hastily scheduled!) tomorrow (Friday) - 4PM - BH212
by Jacobson, Matt 20 Feb '14

20 Feb '14

-- Matt Sent from my iPad Begin forwarded message: From: James Fraser <jaimefraser(a)gmail.com<mailto:jaimefraser@gmail.com>> Date: February 20, 2014 at 6:02:33 PM PST To: "Taunton, Jack (Jack.Taunton(a)ucsf.edu<mailto:Jack.Taunton@ucsf.edu>)" <Jack.Taunton(a)ucsf.edu<mailto:Jack.Taunton@ucsf.edu>>, "Kevan Shokat" <shokat(a)cmp.ucsf.edu<mailto:shokat@cmp.ucsf.edu>>, Natalia Jura <natalia.jura(a)ucsf.edu<mailto:natalia.jura@ucsf.edu>>, "Michael Grabe" <mdgrabe(a)pitt.edu<mailto:mdgrabe@pitt.edu>>, David Sivak <david.sivak(a)gmail.com<mailto:david.sivak@gmail.com>>, "Matthew Jacobson" <matt.jacobson(a)ucsf.edu<mailto:matt.jacobson@ucsf.edu>>, Andrej Sali <sali(a)salilab.org<mailto:sali@salilab.org>>, Jim Wells <Jim.Wells(a)ucsf.edu<mailto:Jim.Wells@ucsf.edu>>, "Lim, Wendell" <Wendell.Lim(a)ucsf.edu<mailto:Wendell.Lim@ucsf.edu>>, Tanja Kortemme <kortemme(a)cgl.ucsf.edu<mailto:kortemme@cgl.ucsf.edu>>, "Fujimori, Danica" <Danica.Fujimori(a)ucsf.edu<mailto:Danica.Fujimori@ucsf.edu>>, Fletterick Robert <flett(a)msg.ucsf.edu<mailto:flett@msg.ucsf.edu>>, Agard Dave <agard(a)msg.ucsf.edu<mailto:agard@msg.ucsf.edu>>, Robert Stroud <stroud(a)msg.ucsf.edu<mailto:stroud@msg.ucsf.edu>>, Trever Bivona <TBivona(a)medicine.ucsf.edu<mailto:TBivona@medicine.ucsf.edu>>, Mark von Zastrow <vonzastrow(a)gmail.com<mailto:vonzastrow@gmail.com>>, "Jeff Cox" <jeffery.cox(a)ucsf.edu<mailto:jeffery.cox@ucsf.edu>> Subject: Cool Kinase Talk (hastily scheduled!) tomorrow (Friday) - 4PM - BH212 Matthew Young (Prof at UMichigan, was a postdoc once upon a time with John Kuriyan) was in town for BPS. He has some cool new mechanistic stories on Kinase regulation (and also some new directions on deubiquitinase inhibitors) that you all might be interested in! The seminar will be at 4PM Friday (tomorrow) in BH212. Please forward to your labs! https://dl.dropboxusercontent.com/u/7403581/matt_young.pdf If you want to meet with Matt, let me know, he'll get to campus around 2:30-3 and be free until 4. I'm happy to direct him your way - first come first served! The plan was to grab a beer after the talk at Terzetto, to which everyone is invited. Hope to see you there! And apologies for the last minute nature of the invite, Jaime ABSTRACT: Matthew Young - University of Michigan Allosteric Regulation Of Protein Kinase Enzymes Via An Electrostatic Switch That Modulates Active Site Dynamics Protein kinase (PK) enzymes are a large family of signaling proteins that play a central role in signal transduction pathways. Robust regulation of their catalytic activity is critical, and many oncogenes harbor mutations that result in misregulated PK activity. The chemical basis for how some PK regulatory factors ultimately affect the rate of chemistry is still not completely understood. We have identified a long-range electrostatic switch that we believe is used by allosteric PK regulatory factors to modulate the rate of chemistry by tuning active-site dynamics. We applied a combination of crystallography, kinetics, and molecular dynamics to determine the chemical kinetic basis for how this electrostatic switch, toggled by regulatory subunit binding, affects each step of the catalytic cycle of CDK2 kinase. We engineered point mutants to deconstruct the kinetic, dynamic, and thermodynamic consequences of the switch. We also evaluated other PKs and find that, although it has evolved to be triggered in different ways by diverse PK regulatory factors, the mechanics of this switch can be conserved. We demonstrate that a key component of the switch is that it affects a significant change in the electrostatic potential within the ATP*Mg binding site of the enzyme. This electrostatic effect is propagated through the low-dielectric protein interior and directly affects the two dominant rate-determining steps of catalysis: attenuating both the recruitment of catalytically essential Mg cofactors (affecting both kcat and KM) as well as the release of the ADP product. Conclusion: We present a chemical hypothesis that provides a mechanistic explanation for one way that a large-scale conformation transition, observed in diverse PK family members, is able to significantly affect the rate of chemistry by acting at a distance from the active site. -- -- James Fraser, PhD Assistant Professor Department of Bioengineering and Therapeutic Sciences Office: N212C Genentech Hall, Lab: N216 Genentech Hall james.fraser(a)ucsf.edu<mailto:james.fraser@ucsf.edu> // jaimefraser(a)gmail.com<mailto:jaimefraser@gmail.com> (415) 493-8421 http://www.fraserlab.com

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