1 1 Dept. of Biophysics Dept. of Biophysics University of Ulm University of Ulm Φ Φ BIO BIO Exploring the Rugged Conformational Energy Exploring the Rugged Conformational Energy Landscape of Proteins Landscape of Proteins Gerd Gerd Ulrich Ulrich Nienhaus Nienhaus Department of Biophysics, University of Ulm, Germany, Department of Biophysics, University of Ulm, Germany, Department of Physics, University of Illinois at Urbana- Department of Physics, University of Illinois at Urbana- Champaign Champaign
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Department of Physics, University of Illinois at Urbana ... · 0.02 0.04 0.06 0.08 0.10 1920 1930 1940 1950 1960 1970 1980 Wavenumber [cm-1] Absorbance [OD] 12 K 200 - 300 K 1920
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11Dept. of BiophysicsDept. of BiophysicsUniversity of UlmUniversity of UlmΦΦBIOBIO
Exploring the Rugged Conformational EnergyExploring the Rugged Conformational EnergyLandscape of ProteinsLandscape of Proteins
GerdGerd Ulrich Ulrich NienhausNienhausDepartment of Biophysics, University of Ulm, Germany,Department of Biophysics, University of Ulm, Germany,Department of Physics, University of Illinois at Urbana-Department of Physics, University of Illinois at Urbana-
ChampaignChampaign
22Dept. of BiophysicsDept. of BiophysicsUniversity of UlmUniversity of UlmΦΦBIOBIO
Proteins - Proteins - ParadigmsParadigms of of ComplexComplex Systems Systems
Systems
• Biomolecules
• Glass-forming liquids
• Synthetic polymers
• Spin glasses
Essential Properties
• Distributed physical parameters
• Wide range of time scales
• Nonlinearity
• Non-Arrhenius temperaturedependence
Disorder:
Frustration:
Spin glass
Rugged energy landscape
?
33Dept. of BiophysicsDept. of BiophysicsUniversity of UlmUniversity of UlmΦΦBIOBIO
ProteinsProteins
• Building blocks:
• Primary structure:
• Secondary structure:
• Tertiary structure:
20 different amino acidsbackbone
sidechain
peptide (covalent) bonds
hydrogen bonds
Sequence determines 3D fold
3D interactions:- hydrophobic- van der Waals- H bonds / ionic / S-SHb
β sheetα helix
44Dept. of BiophysicsDept. of BiophysicsUniversity of UlmUniversity of UlmΦΦBIOBIO
Protein FoldingProtein Folding
• Huge number of possible chainconformations (∼ 10150 for aprotein with 150 amino acids).
• Folding decreases number ofavailable conformationssubstantially.
• The native fold is not unique, butcontains a large number ofconformational substates.
55Dept. of BiophysicsDept. of BiophysicsUniversity of UlmUniversity of UlmΦΦBIOBIO
EnergyEnergy Landscape of Landscape of FoldedFolded Proteins Proteins
E
c c
Sequence
Folding
3D Structure
Conformational substates:same overall structure,details are different.
66Dept. of BiophysicsDept. of BiophysicsUniversity of UlmUniversity of UlmΦΦBIOBIO
Energy Landscape Governs Structure, Dynamics, FunctionEnergy Landscape Governs Structure, Dynamics, Function
2525Dept. of BiophysicsDept. of BiophysicsUniversity of UlmUniversity of UlmΦΦBIOBIO
SummarySummary
•• Proteins Proteins possesspossess a a ruggedrugged energyenergy landscapelandscape•• HugeHuge numbernumber of ~ of ~isoenergeticisoenergetic conformationalconformational substatessubstates•• EnergyEnergy barriersbarriers distributeddistributed in in heightheight
•• DynamicsDynamics on on essentiallyessentially all time all time scalesscales•• DynamicsDynamics overover widewide temperaturetemperature rangerange•• Non-ArrheniusNon-Arrhenius temperaturetemperature dependenciesdependencies
•• HierarchyHierarchy of of SubstatesSubstates•• TaxonomicTaxonomic substatessubstates•• StatisticalStatistical substatessubstates
•• Model Model proteinprotein myoglobinmyoglobin•• EnergyEnergy landscapelandscape explorationexploration byby
•• CryocrystallographyCryocrystallography•• IR IR spectroscopyspectroscopy•• KineticsKinetics
2626Dept. of BiophysicsDept. of BiophysicsUniversity of UlmUniversity of UlmΦΦBIOBIO
AcknowledgmentsAcknowledgments
Andreas OstermannFritz Parak
Alessandro ArcovitoMaurizio Brunori
Aninda BhattacharyyaPengchi DengJan KrieglDon C. LambKarin NienhausCarlheinz RöckerUwe TheilenRobert Waschipky