Dr. Beat Rolf Vögeli

PD Dr. Beat Rolf Vogeli
Laboratory of Physical Chemistry
HCI F217
Swiss Federal Institute of Technology
ETH-Hönggerberg, CH-8093 Zürich, Switzerland

Tel: (+41)-44-633-4405
E-mail: beat.voegeli@phys.chem.ethz.ch
E-mail: beatvoegeli@hotmail.com

Beat

Biomolecular Liquid State Nuclear Magnetic Resonance (NMR) Spectroscopy

'Indeed the protein molecule model resulting from the X-ray crystallographic observations is a "platonic" protein, well removed in its perfection from the kicking and screaming "stochastic" molecule that we infer must exist in solution.'
Weber, G. Adv. Protein Chem., 1975, 29, 1-83.

NMR spectroscopy is one of the principal techniques to answer fundamental questions addressing protein function due to its analytical potential at atomic-level. Our research comprises the development of methods for the determination of 3D structures and dynamics of biomolecules at atomic resolution. Application to proteins and protein complexes will elucidate structure-function and dynamics-function relationships.

Dynamics of Proteins
Proteins are inherently dynamic systems. Their motions cover a large range in magnitude from 10-11 to 10-6 meters and an enormous range of time scales from 10-12 to 102 seconds. Furthermore, Martin Karplus described native proteins as 'surface-molten solids' of which the interior is solid-like but the surface is liquid-like. Since motions are an intrinsic property of molecules, evolution used it for improving protein functions. It is therefore important to elucidate the dynamics-function relationship. For a detailed atomic understanding of a protein function, the 3D atomic-resolution structure and an accurate description of the dynamic behavior are required. Structure determination is well established and NMR relaxation phenomena provide a great deal of insight into local molecular dynamics.

Concerted Motion
Concerted motions may play pivotal roles in processes such as allosteric regulation, channeling, enzyme catalysis, information transmission or molecular recognition. It is well known that domains exhibit fluctuations relatively to one another. There is growing evidence that important molecular processes also involve collective motion of (subdomain) groups of atoms. Correlated internal equilibrium motion has been assessed by methods such as neutron scattering, diffuse X-ray scattering or inelastic Mössbauer scattering. However, only NMR can follow motion site-specifically and at atomic resolution. To date, the picture of concerted motion is incomplete due to the difficulty of separating correlated from uncorrelated motion. For a direct observation, real physical correlation between two bonds is highly requested.

Challenges in NMR today
In contrast to X-ray crystallography, NMR methods provide observation of time-dependent phenomena over a large time-scale. Information about dynamic behavior on time scales up to nanoseconds (fast motion) is commonly collected from measurements of backbone amide relaxation rates and heteronuclear N-H NOEs. Many biologically relevant processes are associated with internal motions taking place at slower time scales. Methods based residual dipolar couplings (RDCs) and Carr-Purcell-Meiboom-Gill (CPMG) measurements have recently been introduced to extend the accessible timescales. Despite their success in characterization of dynamics, all these methods focus on the behavior of isolated bonds, typically N-H. Therefore, concerted dynamics of a larger spin network are still poorly understood. Analysis of side-chain dynamics remains also behind its biological relevance due to the technical challenges in data collection. A consensus picture of motion must properly take into consideration the specific time scales and degrees of correlation. Novel experiments that can distinguish between uncorrelated and correlated motion are therefore required to provide deeper insights into the dynamics of a protein. In addition, systems amenable to routine NMR studies are no larger than 50-100 kDa thus excluding many protein complexes and membrane proteins.

Our Goals
A: Complete Description of the Motional Network in Proteins
Our goal is ultimately to generate movies showing protein or protein complex motion that reflect correctly the timescales of NMR observables. Such an ensemble will reflect correlated and uncorrelated motion in the backbone and side chains.
We are currently developing methods to obtain new input data. First, we are developing a protocol which uses exact Nuclear Overhauser Enhancements (eNOEs) as high accuracy rather than a semi-quantitative inputs in structure and dynamics calculation (average distances are more accurate than 0.1 Angstrom or 10-10 meter). Second, we are showing that cross-correlated relaxation (CCR) rates in combination with RDCs can be used to distinguish between correlated and uncorrelated motion. We are quantifying backbone and side-chain motion in two model proteins, the third IgG-binding domain of the 56-residue protein G (GB3) and the 74-residue human ubiquitin. They are arguably the best-studied proteins in terms of structure and dynamics. Very large sets of RDCs and scalar couplings have already been reported. We are collecting highly accurate CCR rates and NOEs. They will form the most complete high-precision data set in any protein to date. A movie of the spatial sampling of GB3 can be watched here:


We calculated the ensemble with three states. Each state is sampled by five substates obtained from five independent ensemble calculations.
B: Extension of Size Limit
To date, it is difficult to apply routine NMR to systems larger than 50-100 kDa. In practice, many protein complexes and most membrane proteins are excluded from NMR studies. The amide-amide NOE ranks among the most sensitive structural measurables. It can be collected even on very large systems exceeding 500 kDa. We are using our NOE protocol to convert NOEs into quantitative distance restraints for structure calculation. This approach is expected to improve the structural accuracy significantly when only sparse data sets are available.


Education

Habilitation and Venia Legendi in Physical Chemistry, ETH Zürich, 2014

Ph. D. in Natural Sciences (Dr. sc. nat.) at the Institut für Physikalische Chemie, ETH Zürich, 2005

Diploma in Physics (Dipl. phys. ETH) at ETH Zürich (Biophysics and Particle Physics), 2001

Swiss Federal Graduation Diploma, Humanistic Type (Eidgenössische Matura Typus B), 1996


Professional Experience

Privatdozent
Institut für Physikalische Chemie, ETH Zürich, Switzerland, 2014.

Oberassistent
Institut für Physikalische Chemie, ETH Zürich, Switzerland, in the research group of Prof. Roland Riek, 2011-2014.

Post-Doctoral Associate
Institut für Physikalische Chemie, ETH Zürich, Switzerland, in the research group of Prof. Roland Riek, 2008-2011.

Laboratory of Chemical Physics, National Institute of Diabetes, Digestive & Kidney Diseases (NIDDK) of the National Institutes of Health (NIH), Bethesda, Maryland, USA in the research group of Dr. A. Bax, 2005-2008.

Research Fellow
Institut für Physikalische Chemie, ETH Zürich, Switzerland in the research group of Prof. K. Pervushin, 2001-2005

Institute of Molecular Biology and Biophysics, ETH Zürich, Switzerland in the research group of Prof. K. Wüthrich, 2000-2001

Industrial Collaboration
Bruker BioSpin AG, Fällanden, Switzerland 2002-2005


Publications

* equal contribution

Nikolaos G. Sgourakis, Kannan Natarajan, Jinfa Ying, Beat Vögeli, Lisa F. Boyd, David H. Margulies & Ad Bax
The Structure of Mouse Cytomegalovirus m04 Protein Obtained from Sparse NMR Data Reveals a Conserved Fold of the m02-m06 Viral Immune Modulator Family
2014, Structure, DOI: 10.1016/j.str.2014.05.018. PDF download Supp info

Simon Olsson, Vögeli, Andrea Cavalli, Wouter Boomsma, Jesper Ferkinghoff-Borg, Kresten Lindorff-Larsen & Thomas Hamelryck
Probabilistic Determination of Native State Ensembles of Proteins
2014, J. Chem. Theory Comput., 10, 3484-3491. PDF download Supp info

Beat Vögeli, Julien Orts, Dean Strotz, Celestine Chi, Martina Minges, Marielle Aulikki Wälti, Peter Güntert & Roland Riek
Towards a True Protein Movie: A Perspective on the Potential Impact of the Ensemble-based Structure Determination Using Exact NOEs
2014, J. Magn. Reson., 241, 53-59. PDF download

Beat Vögeli
The Nuclear Overhauser Effect from a Quantitative Perspective
2014, Prog. Nucl. Magn. Reson. Spectrosc., 78, 1-46. PDF download

Julien Orts, Beat Vögeli, Roland Riek & Peter Güntert
Stereospecific Assignments in Proteins Using Exact NOEs
2013, J. Biomol. NMR, 57, 211-218. PDF download Supp info

Beat Vögeli
Full Relaxation Matrix Analysis of Apparent Cross-Correlated Relaxation Rates in Four-Spin Systems
2013, J. Magn. Reson., 226, 52-63. PDF download Supp info Mathematica script for pulse sequence 1C, HN-N/HN-N CCR Mathematica script for pulse sequence 1A, HN-N/HA-CA CCR Mathematica script for pulse sequence 1B, HN-N/HA-CA CCR Mathematica script for pulse sequence 2A, HN-N/HA-CA CCR

Beat Vögeli, Julien Orts, Dean Strotz, Peter Güntert & Roland Riek
Discrete Three-Dimensional Representation of Macromolecular Motion from eNOE-Based Ensemble Calculation
2012, Chimia, 66, 787-790. PDF download

Beat Vögeli, Peter Güntert & Roland Riek
Multiple-state Ensemble Structure Determination from eNOE Spectroscopy
2013, Mol. Phys., 111, 437-454. PDF download Supp info

Beat Vögeli, Sina Kazemi, Peter Güntert & Roland Riek
Spatial Elucidation of Motion in Proteins by Ensemble-Based Structure Calculation Using Exact NOEs
2012, Nat. Struct. Mol. Biol., 19, 1053-1057. PDF download Supp text & figs Supp tables

Julien Orts, Beat Vögeli & Roland Riek
Relaxation Matrix Analysis of Spin Diffusion for the NMR Structure Calculation with eNOEs
2012, J. Chem. Theory Comput., 8, 3483-3492. PDF download Supp info

Beat Vögeli
How Uniform is the Peptide Plane Geometry? A High-Accuracy NMR Study of Dipolar CAC'/HNN Cross-Correlated Relaxation
2011, J. Biomol. NMR, 50, 315-329. PDF download Supp info

Dominik Leitz, Beat Vögeli, Jason Greenwald & Roland Riek
Temperature Dependence of 1HN-1HN Distances in Ubiquitin As Studied by Exact Measurements of NOEs
2011, J. Phys. Chem. B, 115, 7648-7660. PDF download Supp info

Beat Vögeli
Comprehensive Description of NMR Cross-Correlated Relaxation under Anisotropic Molecular Tumbling and Correlated Local Dynamics on All Timescales
2010, J. Chem. Phys., 133, 014501. PDF download

Selected for issue cover.
Selected for the Virtual Journal of Biological Physics Research, 2010, 20:1. view

Beat Vögeli, Michael Friedmann, Dominik Leitz, Alexander Sobol & Roland Riek
Quantitative Determination of NOE Rates in Perdeuterated and Protonated Proteins: Practical and Theoretical Aspects
2010, J. Magn. Reson., 204, 290-302. PDF download Supp info

Beat Vögeli & Roland Riek
Side Chain-Backbone Projections in Aromatic and ASX Residues from NMR Cross-Correlated Relaxation
2010, J. Biomol. NMR, 46, 135-147. PDF download Bruker pp 3D ct-MQ(Cb,N)-HN(CA)CB for HNN/CbCg CCR Bruker pp 3D ct-MQ(Cb,N)-HN(COCA)CB for HNN/CbCg CCR

Beat Vögeli, Takuya Segawa, Dominik Leitz, Alexander Sobol, Alexandra Choutko, Daniel Trzesniak, Wilfred Van Gunsteren & Roland Riek
Exact Distances and Internal Dynamics of Perdeuterated Ubiquitin from NOE Buildups
2009, J. Am. Chem. Soc., 131, 17215-17225. PDF download Supp info

Beat Vögeli & Lishan Yao
Correlated Dynamics between Protein HN and HC Bonds Observed by NMR Cross Relaxation
2009, J. Am. Chem. Soc., 131, 3668-3678. PDF download Supp info NIH Public Access Bruker pp 3D ct-MQ(Ca,N)-HNCA for HNN/CaHa CCR Bruker pp 3D ct-MQ(Ca,N)-HN(CO)CA for HNN/CaHa CCR

Lishan Yao, Beat Vögeli, Jinfay Ying & Ad Bax
NMR Determination of Amide N-H Equilibrium Bond Length from Concerted Dipolar Coupling Measurements
2008, J. Am. Chem. Soc., 130, 16518-20. PDF download Supp info NIH Public Access

Beat Vögeli, Lishan Yao & Ad Bax
Protein Backbone Motion Viewed by Intraresidue and Sequential HN-Ha Residual Dipolar Couplings
2008, J. Biomol. NMR, 41, 17-28. PDF download Supp info NIH Public Access

Lishan Yao, Beat Vögeli, Dennis Torchia & Ad Bax
Simultaneous NMR Study of Protein Structure and Dynamics Using Conservative Mutagenesis
2008, J. Phys. Chem. B, 121, 6045-6056. PDF download Supp info

Konstantin Pervushin, Katherina Vamvaca*, Beat Vögeli* & Donald Hilvert
Structure and Dynamics of an Enzymatically Active Molten Globule
2007, Nat. Struct. Mol. Biol, 14, 1202-1206. PDF download Supp info PDB view

Beat Vögeli, Jinfa Ying, Alexander Grishaev & Ad Bax
Limits on Variations in Protein Backbone Dynamics from Precise Measurements of Scalar Couplings
2007, J. Am. Chem. Soc., 129, 9377-9385. PDF download Supp info

Kaifeng Hu, Beat Vögeli & G. Marius Clore
Spin-State Selective Carbon-Detected HNCO with TROSY Optimization in All Dimensions and Double Echo-Antiecho Sensitivity Enhancement in Both Indirect Dimensions
2007, J. Am. Chem. Soc., 129, 5484-5491. PDF download Supp info

Kaifeng Hu*, Beat Vögeli* & G. Marius Clore
13C-Detected HN(CA)C and HMCMC Experiments Using a Single Methyl-Reprotonated Sample for Unambiguous Methyl Resonance Assignment
2006, J. Biomol. NMR, 36, 259-266. PDF download

Kaifeng Hu*, Beat Vögeli* & G. Marius Clore
Interference between Transverse Cross-Correlated Relaxation and Longitudinal Relaxation Affects Apparent J-Coupling and Transverse Cross-Correlated Relaxation
2006, Chem. Phys. Lett., 423, 123-125. PDF download

Donghan Lee, Beat Vögeli & Konstantin Pervushin
Detection of C',CA Correlations in Proteins Using a New Time- and Sensitivity-Optimal Experiment
2005, J. Biomol. NMR, 31, 273-278. PDF download Supp info

Beat Vögeli
Towards Structure and Dynamics of Large and Dynamically Disordered Biomacromolecules: New Methods in Solution NMR Spectroscopy
2005, ETH Z
ürich, Diss. ETH No. 15993. PDF download

Kaifeng Hu, Beat Vögeli & Konstantin Pervushin
Side-Chain H and C Resonance Assignment in Protonated / Partially Deuterated Proteins Using an Improved 3D 13C-Detected HCC-TOCSY
2005, J. Magn. Reson., 174, 200-208. PDF download

Beat Vögeli, Helena Kovacs & Konstantin Pervushin
Simultaneous 1H- or 2H-, 15N- and Multiple-Band-Selective 13C-Decoupling during Acquisition in 13C-Detected Experiments with Proteins and Oligonucleotides
2005, J. Biomol. NMR, 31, 1-9. PDF download

Konstantin Pervushin, Beat Vögeli, Tim Heinz & Philippe Hünenberger
Measuring 1H-1H and 1H-13C RDCs in Methyl Groups: Example of Pulse Sequences with Numerically Optimized Coherence Transfer Schemes
2005, J. Magn. Reson., 172, 36-47. PDF download Supp info 1 Supp info 2

Katherina Vamvaca, Beat Vögeli, Peter Kast, Konstantin Pervushin & Donald Hilvert
An Enzymatic Molten Globule: Efficient Coupling of Folding and Catalysis
2004, Proc. Natl. Acad. Sci. USA, 101, 12860-12864. PDF download Supp info

Selected for Editors' Choice: Highlights of the Recent Literature
Biochemistry: One Size Fits Many
2004, Science, 305, 5691-5691. PDF download

Beat Vögeli, Helena Kovacs & Konstantin Pervushin
Measurements of Side-Chain 13C-13C Residual Dipolar Couplings in Uniformly Deuterated Proteins
2004, J. Am. Chem. Soc., 126, 2414-2420. PDF download Supp info

Konstantin Pervushin & Beat Vögeli
Observation of Individual Transitions in Magnetically Equivalent Spin Systems
2003, J. Am. Chem. Soc., 125, 9566-9567. PDF download Supp info

Beat Vögeli & Konstantin Pervushin
TROSY Experiment for Refinement of Backbone psi and phi by Simultaneous Measurements of Cross-Correlated Relaxation Rates and 3,4JHaHN Coupling Constants
2002, J. Biomol. NMR, 24, 291-300. PDF download

Konstantin Pervushin, Beat Vögeli & Alexander Eletsky
Longitudinal 1H Relaxation Optimization in TROSY NMR Spectroscopy
2002, J. Am. Chem. Soc., 124, 12898-12902. PDF download Supp info

Beat Vögeli, Roland Riek (Supervisor) & Kurt Wüthrich (Supervisor)
NMR Solution Structure of the Fragments of the Human Prion Protein hPrP(121-226) and hPrP(130-230)
2001, Diploma Thesis, ETH Zürich.