computational biophysics: introduction · 2016. 10. 24. · computational biophysics: introduction...
TRANSCRIPT
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Computational Biophysics: Introduction
Bert de Groot, Jochen Hub, Helmut Grubmüller
Max Planck-Institut für biophysikalische Chemie Theoretische und Computergestützte Biophysik Am Fassberg 11 37077 Göttingen
Tel.: 201-2308 / 2314 / 2301 / 2300 (Secr.)
Email: [email protected] [email protected] [email protected] www.mpibpc.mpg.de/grubmueller/
mailto:[email protected]
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Chloroplasten, Tylakoid-Membran
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Primary steps in photosynthesis
From: X. Hu et al., PNAS 95 (1998) 5935
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F-ATP Synthase
20 nm
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F1-ATP(synth)ase
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ATP hydrolysis drives rotation of γ subunit and attached actin filament
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F1-ATP(synth)ase
NO INERTIA!
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The Ribosome
30 nm
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Proteins are Molecular Nano-Machines !Elementary steps:
Conformational motions
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Overview: Computational Biophysics: Introduction
L1/P1: Introduction, protein structure and function, molecular dynamics, approximations, numerical integration, argon
L2/P2: Tertiary structure, force field contributions, efficient algorithms, electrostatics methods,
protonation, periodic boundaries, solvent, ions, NVT/NPT ensembles, analysis
L3/P3: Protein data bank, structure determination by NMR / x-ray; refinement
L4/P4: Bioinformatics: sequence alignment, Structure prediction, homology modelling
L5/P5: Monte Carlo, normal mode analysis, principal components
L6/P6: Charge transfer & photosynthesis, electrostatics methods
L7/P7: Aquaporin / ATPase / Ribosome: examples from current research
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Overview: Computational Biophysics: Concepts & Methods
L08/P08: MD Simulation & Markov Theory: Molecular Machines
L09/P09: Free energy calculations: Molecular recognition
L10/P10: Non-equilibrium thermodynamics: Molecular driving forces
L11/P11: Quantum mechanics methods: Enzymatic catalysis
L12/P12: Hartree-Fock, density functional theory
L13/P13: Rate theory: Biomolecular efficiency
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a water molecule
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an ethanol molecule
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a water droplet
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a water droplet
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water vapor
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a salt crystal (NaCl)
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bovine pancreatic trypsin inhibitor (BPTI)
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20 different amino acids
Alanine
Tyrosine Cysteine
Arginine
Asparagine
Aspartate
Glutamate
Glycine
Threonine
Lysine
Glutamine TryptophaneMethionine
Histidine
Phenylalanine
Valine
Proline
Isoleucine
Serine
Leucine
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hexa-peptide
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alpha-helix
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beta sheet
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bovine pancreatic trypsin inhibitor (BPTI)
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myoglobin
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antibody IGG domain
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porin
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bacteriorhodopsin
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?
Four different nucleotides encode amino acids
(à Uracil)
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hemagglutinin (influenza virus)
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hemagglutinin (influenza virus)
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Molecular Dynamics Simulations
Interatomic interactions
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Molecular Dynamics SimulationMolecule: (classical) N-particle system
Newtonian equations of motion:
with
Integrate numerically via the „leapfrog“ scheme:
(equivalent to the Verlet algorithm)
with
Δt ≈ 1fs!
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MD-Experiments with Argon Gas
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Radial distribution function
300 K 70 K 10 K
distance
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i~@t (r, R) = H (r, R)
He e(r;R) = Ee(R) e(r;R)
Molecular Dynamics Simulations
Schrödinger equation
Born-Oppenheimer approximation
Nucleic motion described classically
Empirical Force field
1
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Molecular dynamics-(MD) simulations of Biopolymers• Motions of nuclei are described classically,
• Potential function Eel describes the electronic influence on motions of the nuclei and is approximated empirically à „classical MD“:
approximated
exact
Eibond
|R|ν0
KBT {
Covalent bonds Non-bonded interactions
==R
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Molecular Dynamics SimulationMolecule: (classical) N-particle system
Newtonian equations of motion:
with
Integrate numerically via the „leapfrog“ scheme:
(equivalent to the Verlet algorithm)
with
Δt ≈ 1fs!
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„Force-Field“
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Computational task:
Solve the Newtonian equations of motion:
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BPTI: Molecular Dynamics (300K)
8
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4 nm
Molecular dynamics simulation, 1s = 2 ·10 -11s ^