Self Organization in Biomolecular Systems

Simulating the folding and aggregation of peptides proteins and lipids.

Alan E. MarkSchool of Molecular Microbial Sciences

a.e.mark@uq.edu.au

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