Self Organization in Biomolecular Systems
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Transcript of Self Organization in Biomolecular Systems
Self Organization in Biomolecular Systems
Simulating the folding and aggregation of peptides proteins and lipids.
Alan E. MarkSchool of Molecular Microbial Sciences
Periodic Boundary Conditions
water
Molecular Dynamics A molecular force field describing the inter-atomic interactions
(underlying model)
jijipairs
torsions
torsions
anglesbondsbN
rqqrjiCrjiC
nK
K
KbbKrrrV
jiji ,06
612
12
20
20
2021
4/]/),(/),([
)]cos(1[2
1
)(2
1
)(2
1)(
2
1),...,,(
,,επε
δφ
ξξ
θθ
φ
ξ
θ
+−+
+++
−+
−+−=
∑
∑
∑
∑∑
Solve Newton’s equations of motionTime evolution of the system
(classical mechanics)
),...,,( 21
2
2
Ni
i
i
ii
rrrVr
F
m
F
dt
rd
∂∂
−=
=
Self Organization in Biomolecular SystemsSimulating the folding and aggregation of peptides proteins and lipids.
Thermodynamic Properties of BiomoleculesFree energy calculations, ligand design, force field refinement.
Protein Structure Prediction and Refinement
Structural Proteomics.
Non-equilibrium protein dynamics Signal transduction, cell surface receptors, mechanoselective pores.
• The Model (force field)The model must encompass the property of interest
•Time Scale. The simulation time >> time scale of the process to be investigated
Factors that Determine Reliability
• The Model (force field)Is the model fitted to the property of interest?
•Time Scale. Is the process spontaneous or enforced?
•Know what is reality.Are we fitting to just another model?
To Match Reality
Folding and aggregation of peptides and proteins.
Self Organization in Biomolecular Systems 1.
Beta-peptides
Betanova
EPOVPAL
Acknowledgements
Folding and aggregation of peptides and proteins.
Self Organization in Biomolecular Systems 2.
-Peptides
helicalpeptides
CoiledCoils
WWdomain
Beta-peptideRep-exchange
Acknowledgements
SIVgp32
Acknowledgements
Folding and aggregation of peptides and proteins.
Self Organization in Biomolecular Systems 3.
SUP35
SH3transition
states
Acknowledgements
Folding and aggregation of peptides and proteins.
Self Organization in Biomolecular Systems 4.
Foldingrates
Spontaneous Aggregation of Lipids and Surfactant Systems
Self Organization in Biomolecular Systems 5.
Vesicle Formation
BilayerFormation
VesicleFusion
Phase Transition
CC
DomainFormation
Phase Transition
AA
Acknowledgements
IsopreneResorcinol
Spontaneous Aggregation of Membrane Protein Systems
Self Organization in Biomolecular Systems 6.
PeptidePores Equ II W112
Acknowledgements
Acknowledgements
PYP
Particle Migration
TRAIL_DR5
TRAIL
Non-equilibrium dynamics Signal transduction, cell surface receptors, mechanoselective pores.
Protein Structure Prediction and Refinement
MDStructure
Refinement
Acknowledgements
SolventOscillation
I
ADP ADPChaperone Cage
Folding of HydrophobinRonen Zangi
Hari Leontiadou Marcel L. Vocht (Biomade)George Robillard (Biomade)
Stability of BetanovaPatricia Soto
Danilo Roccatano (Rome)Giorgio Colombo (Milan)
Luis Serrano (EMBL)Manuela Lopez de la Paz (EMBL)
Spontaneous Aggregation of LipidsSiewert-Jan Marrink
Alex de VriesPeter Tieleman (Calgary)Eric Lindahl (Sweden)
Aggregation of EPOGilles Pieffet
Structure RefinementFan HaoYing Xu
Activation of Death Receptor DR5Tjserk WassenaarWin Quax (RUG)
Activation of Photoactive Yellow ProteinGerrit Groenhof
Mike Rob (London)
Thrombin InhibitorsAlessandra Villa
Ronen ZangiGilles Pieffet
Field Induced Particle MigrationVolker Knecht
Siewert-Jan MarrinkJan Engberts (RUG)
Activation of Dengue VirusDaniela Müller Bostjan Kobe
Thorsten KampmannPaul Young
Aggregation of Amyloid Peptides
Xavier PerioleAldo Ramponi
Patrica SotoMchele Vendruscolo (Cambridge)
Spontaneous Pore formationSiewert-Jan Marrink
Hari LeontiadouDurba Sengupta
David Poger
Major Funding
GBBGBB