biochemie iv – struktur und dynamik von biomolekülen ii. (mittwochs 8-10 h, inf 230, klhs)...
TRANSCRIPT
![Page 1: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/1.jpg)
Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS)
30.4. Jeremy Smith: Intro to Molecular Dynamics Simulation.7.5. Stefan Fischer: Molecular Modelling and Force Fields.14.5. Matthias Ullmann: Current Themes in Biomolecular Simulation.21.5. Ilme Schlichting: X-Ray Crystallography-recent advances (I).28.5. Klaus Scheffzek: X-Ray Crystallography-recent advances (II).4.6. Irmi Sinning: Case Study in Protein Structure.11.6. Michael Sattler: NMR Applications in Structural Biology.18.6. Jörg Langowski: Brownian motion basics.25.6. Jörg Langowski: Single Molecule Spectroscopy.2.7. Karsten Rippe: Scanning Force Microscopy.9.7. Jörg Langowski: Single Molecule Mechanics.16.7. Rasmus Schröder: Electron Microscopy.23.7. Jeremy Smith: Biophysics, the Future, and a Party.
![Page 2: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/2.jpg)
Universität Heidelberg
Protein
Computational Computational Molecular BiophysicsMolecular Biophysics
![Page 3: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/3.jpg)
IBM today will announce its intention to invest $100 million overthe next five years to build Blue Gene, a supercomputer that willbe 500 times faster than current supercomputing technology.Researchers plan to use the supercomputer to simulate thenatural biological process by which amino acids fold themselvesinto proteins. (New York Times 12/06/99)
IBM PLANS SUPERCOMPUTER THAT WORKS AT SPEED OF
LIFE
![Page 4: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/4.jpg)
Protein Folding
Exploring the Folding Landscape
![Page 5: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/5.jpg)
Uses of Molecular Dynamics Simulation:
•structure•flexibility•solvent effects•chemical reactions•ion channels•thermodynamics (free energy changes, binding)•spectroscopy•NMR/crystallography
![Page 6: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/6.jpg)
Atomic-Detail Computer Simulation
Model System
Molecular Mechanics Potential
ji ij
ji
ji ij
ij
ij
ijij
impropersdihedrals
N
n
n
anglesbondsb
Dr
rr
KnK
kbbkV
,,
612
20
1
20
20
4
cos1
Energy Surface Exploration by Simulation..
![Page 7: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/7.jpg)
Model System
•set of atoms•explicit/implicit solvent•periodic boundary conditions
Potential Function
•empirical•chemically intuitive•quick to calculate
Tradeoff: simplicity (timescale) versus accuracy
![Page 8: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/8.jpg)
Lysozyme in explicit water
![Page 9: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/9.jpg)
2/8MM Energy Function
l
r
qi qj
![Page 10: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/10.jpg)
Newton’s Law:Newton’s Law:
i
ii r
VF
iii amF
Potential Function Force
![Page 11: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/11.jpg)
Taylor expansion:
Verlet’s Method
![Page 12: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/12.jpg)
![Page 13: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/13.jpg)
Ensemble AverageObservable
StatisticalMechanics
1 hour here
1 hour here
![Page 14: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/14.jpg)
Ergodic Hypothesis:MD Simulation:
![Page 15: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/15.jpg)
Analysis of MD
ConfigurationsAveragesFluctuationsTime Correlations
![Page 16: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/16.jpg)
Molecular dynamics:Integration timestep - 1 femtosecondSet by fastest varying force.Accessible timescale about 10 nanoseconds.
Bond vibrations - 1 fsCollective vibrations - 1 psConformational transitions - ps or longerEnzyme catalysis - microsecond/millisecondLigand Binding - micro/millisecondProtein Folding - millisecond/second
Timescales.
![Page 17: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/17.jpg)
•SOME EXAMPLES
![Page 18: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/18.jpg)
![Page 19: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/19.jpg)
![Page 20: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/20.jpg)
![Page 21: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/21.jpg)
![Page 22: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/22.jpg)
11 Sequences in 9 clades
• A1 LEU PRO CYS ARG ILE LYS GLN PHE ILE ASN MET TRP GLN GLU VAL +2• B1 LEU PRO CYS ARG ILE LYS GLN ILE VAL ASN MET TRP GLN GLU VAL +2• C1 ILE PRO CYS ARG ILE LYS GLN ILE ILE ASN MET TRP GLN GLU VAL +2• D2 LEU PRO CYS ARG ILE LYS PRO ILE ILE ASN MET TRP GLN GLU VAL +2• E2 LEU PRO CYS LYS ILE LYS GLN ILE ILE ASN MET TRP GLN GLY VAL +3• E3 LEU PRO CYS LYS ILE LYS GLN ILE ILE LYS MET TRP GLN GLY VAL +4• F1 LEU LEU CYS LYS ILE LYS GLN ILE VAL ASN LEU TRP GLN GLY VAL +2• G2 LEU PRO CYS LYS ILE LYS GLN ILE VAL ARG MET TRP GLN ARG VAL +5• 1A0 LEU PRO CYS LYS ILE LYS GLN ILE VAL ASN MET TRP GLN ARG VAL +4• 2A3 LEU GLN CYS ARG ILE LYS GLN ILE VAL ASN MET TRP GLN LYS VAL +4• OC4 ILE PRO CYS LYS ILE LYS GLN VAL VAL ARG SER TRP ILE ARG GLY +5
Does CD4-binding peptide have a similar
structure in all strains of HIV-1 ?
![Page 23: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/23.jpg)
Molecular Dynamics Simulation Setup
• Box dimensions: 53x40x40 Ǻ• Explicit water molecules (TIP3P)
(~8600 atoms)• Explicit ions
(Sodium and Chloride, 26 ions in total);physiological salt: 0.23M
• ~240 peptide atoms=> approx. 8900 atoms in total
• Uncharged system• NPT ensemble: 300K, 1atm• 5ns simulation time for each strain
=> 55ns total simulation time
![Page 24: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/24.jpg)
Dihedral angles
![Page 25: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/25.jpg)
Surface electrostatic properties conserved.
![Page 26: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/26.jpg)
Detection of Individual p53-Autoantibodies in Human Sera
Cancer Biotechnology.
![Page 27: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/27.jpg)
Rhodamine 6G
![Page 28: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/28.jpg)
O H
N
O
O
N
N
MR121
Fluorescence Quenching of Dyes by Trytophan
Dye
Quencher
![Page 29: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/29.jpg)
Fluorescently labeled Peptide
?
![Page 30: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/30.jpg)
Analysis
r
![Page 31: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/31.jpg)
![Page 32: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/32.jpg)
Strategy:
Quenched Fluorescent
Results:
HealthyPersonSerum
CancerPatientSerum
![Page 33: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/33.jpg)
Protein Folding/Unfolding
![Page 34: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/34.jpg)
Protein Folding
Exploring the Folding Landscape
![Page 35: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/35.jpg)
BSE cattle bovine spongiform encephalopathy scrapie sheepCWD elk chronic wasting disease TME mink transmissible mink encephalopathy
kuru human
CJD human Creutzfeldt-Jakob disease sporadic
genetic
infectious
vCJD human variant CJD
GSS human Gerstmann-Sträussler-Scheinker disease
FFI human fatal familial insomnia
Prion diseases of animal and man
![Page 36: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/36.jpg)
Properties of the prion protein
- The natural prion protein is encoded by a single exon as a polypeptide chain of about 250 to 260 amino acid residues.
- Posttranslational modification: cleavage of a 22 (N-terminal) and 23 (C-terminal) residue signal sequence => about 210 amino acid residues
- PrP contains a single disulfide bridge.
- PrP contains 2 glycosylation sites.
- PrP inserts into the cellular plasma membrane through a glycosyl-phosphatidyl-inositol anchor at the C-terminus.
![Page 37: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/37.jpg)
Structure of the prion protein
![Page 38: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/38.jpg)
Superimposed PrP structures
The first image below shows the structure of part of the hamster and mouse PrPC molecules superimposed. The close similarity in the structures is obvious, as is the preponderance of alpha helical structure.
![Page 39: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/39.jpg)
Location of human mutations
The picture shows the position of various mutations important for prion disease development in humans modelled on the hamster structure PrPC.
Many of these mutations are positioned such that they could disrupt the secondary structure of the molecule.
![Page 40: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/40.jpg)
Mouse Prion Protein (PrPc)
NMR Structure
![Page 41: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/41.jpg)
![Page 42: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/42.jpg)
![Page 43: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/43.jpg)
Structure of PrPSc
The PrPSc has a much higher -sheet content.
![Page 44: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/44.jpg)
Bundeshochleistungsrechner Hitachi SR8000-F1
![Page 45: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/45.jpg)
IBM today will announce its intention to invest $100 million overthe next five years to build Blue Gene, a supercomputer that willbe 500 times faster than current supercomputing technology.Researchers plan to use the supercomputer to simulate thenatural biological process by which amino acids fold themselvesinto proteins. (New York Times 12/06/99)
IBM PLANS SUPERCOMPUTER THAT WORKS AT SPEED OF
LIFE
![Page 46: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/46.jpg)
Safety in Numbers
![Page 47: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/47.jpg)
![Page 48: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/48.jpg)
![Page 49: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/49.jpg)
![Page 50: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/50.jpg)
Large-Scale Conformational Change
![Page 51: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/51.jpg)
Structural Changes in Proteins:The Physical Problem
ENERGY LANDSCAPE: high-dimensional, rugged.
Need to find PATHWAY WITH LOWEST SADDLE POINT.
![Page 52: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/52.jpg)
Conformational Pathways
Navigate energy landscape to find continuous path of lowest free energy from one end point to the other.
`
![Page 53: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/53.jpg)
Thick filament
Muscle Contraction
of Myosin and ActinSliding filaments….
Thin filament
Z disc
![Page 54: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/54.jpg)
ATP Hydrolysis by Myosin
SONJA SCHWARZLSTEFAN FISCHER
![Page 55: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/55.jpg)
Power Stroke in Muscle Contraction.
![Page 56: Biochemie IV – Struktur und Dynamik von Biomolekülen II. (Mittwochs 8-10 h, INF 230, klHS) 30.4.Jeremy Smith: Intro to Molecular Dynamics Simulation. 7.5.Stefan](https://reader038.vdokument.com/reader038/viewer/2022103004/56649cb15503460f9497619a/html5/thumbnails/56.jpg)
End ss 2003