EINFÜHRUNG IN DIE BIOPHYSIK

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1 EINFÜHRUNG IN DIE BIOPHYSIK Helmut Grubmüller, Detlev Schild Max Planck-Institut für biophysikalische Chemie Theoretische und Computergestützte Biophysik Am Fassberg Göttingen Tel.: / hgrubmu@gwdg.de

2 (A) Molekularer Level (H. Grubmüller) 1. Einführung 1.1. Beispiele für Proteinfunktion: Photosynthese, ATP-Synthese 1.2. The players: DNA/RNA, Proteine, Enzyme, Ribosom, Lipide, Kohlehydrate, Lösung, kleine Moleküle (Ionen, ATP, Vitamine, Farbstoffe) 1.3. Molekulare Evolution: Woher kommt das alles? 2. Proteinstruktur und vielfältige Wechselwirkungen 2.1. Proteinstruktur: Aminosäuren, Primär-, Sekundär-, Tertiär-, Quartär-Struktur 2.2. Inter-/ Intramolekulare Wechselwirkungen und deren Stärke 2.3. Zusammenhang Proteinstruktur/Proteinsequenz; Homologie, Proteinfamilien, Bioinformatik 2.4. Experimentelle Methoden: PCR, Sequenzierung, Gel-elektrophorese, X-ray, EM, NMR

3 3. Proteindynamik 3.1. Dynamische Prozesse, Zeitskalen 3.2. Freie Energie, Ligandenbindung, Drug design 3.3. Experimentelle Methoden: EPR, Neutronenstreuung, FT-IR, opt. Spektr., AFM, FRET, Patch Clamp 4. Mechanismen der Proteinfunktion 4.1. ATP-Synthese: Elektro-Mechano-Chemische Energiewandlung 4.2. Wasserpermeation über Poren-Proteine: ein bemerkenswerter Filter 4.3. BSE, Kreutzfeld-Jakob

4 (B) Zellulärer Level (D. Schild) A) Elektrochemische GGW an Zellmembranen (Donnan-GGW, Membranpotentiale) B) Transportproteine (ATP, gradient driven), Struktur, Funktion, Elektrochemie, Beispiel: KNaATPase, NaCaAntiport C) Ionenkanäle (Struktur, Selektivität, Permeabilität, Spannungsabhängigkeit, GHK, HodgkinHuxleyGl.) D) Kabelgleichungen (elekroton. Leitung), Aktionspot. (Nerv, Muskel, Herz) E) Nervenleitung F) Synaptische Signalverarbeitung (Exocytose, Transmitter, Rezeptoren) G) Calcium: Wirkungen, Wellen, Pufferung, Messung H) Biophysik des Sehens & Photobiophysik I) Biophysik des Hörens, Psychoakustik J) Chemische Sinne: biol. and artificial nose K) Molekulare Motoren (Kinesin, Dynein, Myosin/Aktin)

5 Begleitend: Computersimulation Biomolekularer Prozesse (H. Grubmüller, B. de Groot, Di, 15:00-16:30, HS3) - Biomolekulare Energetik & Thermodynamik - Intra- und Intermolekulare Wechselwirkungen - Proteindynamik und Proteinfunktion - hands-on - Molekuardynamiksimulationen

6 MD simulations of water transport via aquaporins - ca atoms - full electrostatics, periodic boundary - 10 ns simulation time B.L. de Groot, H. Grubmüller, Science 294, 2353 (2001)

7 Molecular dynamics simulation, 1s = ^ s 4 nm

8 Water Permeation proceeds in steps one out of 16 full spontaneous permeation events (2 ns) (outside the channel, only few water molecules are shown) B.L. de Groot, H. Grubmüller, Science 294, 2353 (2001)

9 Chloroplasten, Tylakoid-Membran

10 From: X. Hu et al., PNAS 95 (1998) 5935 Primary steps in photosynthesis

11 12 nm Photosynthetic Reaction Center

12 a water molecule

13 an ethanol molecule

14 a water droplet

15 a water droplet

16 water vapor

17 a salt crystal (NaCl)

18 diamond (10-21 carat)

19 Carbon Oxygen Nirogen Sulfur (Hydrogen not shown) Photosynthetic Reaction Center

20 Carbon Oxygen Nirogen Sulfur (Hydrogen not shown) Photosynthetic Reaction Center

21 Carbon Oxygen Nirogen Sulfur (Hydrogen not shown) Photosynthetic Reaction Center

22 Subunits without covalent linkage Photosynthetic Reaction Center

23 Subunits without covalent linkage Photosynthetic Reaction Center

24 only amino acids shown Photosynthetic Reaction Center

25 backbone with side groups: aliphatic aromatic charged others Photosynthetic Reaction Center

26 backbone fold Photosynthetic Reaction Center

27 secondary structure Photosynthetic Reaction Center

28 alpha helices beta sheets unstructured and loops Photosynthetic Reaction Center

29 Prosthetic groups: Chlorophyl ( with Mg++) Photosynthetic Reaction Center

30 Prosthetic groups: more chlorophyls and pheophytins Photosynthetic Reaction Center

31 Prosthetic groups: Menaquinone Iron Ubiquinone Photosynthetic Reaction Center

32 Prosthetic groups: Heme groups with iron Photosynthetic Reaction Center

33 Proteins contain water molecules Photosynthetic Reaction Center

34 Primary steps in photosynthesis

35 light harvesting complex

36 Proteins only (apoprotein) light harvesting complex II

37 Proteins only light harvesting complex II

38 + chlorophyls, carotenoids light harvesting complex II

39 Primary steps in photosynthesis

40 F-ATP Synthase

41 ATP hydrolysis drives rotation of γ subunit and attached actin filament

42 Photosynthetic Reaction Center

43

44 The Cell?

45 Hexokinase W. S. Bennet and T. A. Steitz, JMB 140, 211

46 Electrostatics of Acetylcholinesterase Acetylcholinesterase is an electrostatic vacuum cleaner Ripoll et al., PNAS 90 (1993), 5128

47 myoglobin

48 antibody IGG domain

49

50 porin

51 bacteriorhodopsin

52 A model of Bacteriorhodopsin

53 A model for the BR photocycle

54 Influenza Virus Infection

55 hemagglutinin (influenza virus)

56 Conformational Transition of Hemagglutinin