One step beyond: Simulation of peptide aggregationOne step beyond: Simulation of peptide aggregation

Viral fusogenic activity

Simian Immunodeficiency Virus (SIV) envelope

glycoprotein precursor gp160

Surface glycoprotein gp120

Transmembrane glycoprotein gp32

Proteolytic cleavage

12-residue N-terminal region of SIV-gp32 (SIVwt): NH

2-G V F V L G F L G F L A

ATR-IR1 and ThioflavinT fluorescence2

sheet aggregates depending on peptide concentration.

1. Martin, I. et al. Journal of Virology, 1994, 68, 11392. Cladera, J. et al. Journal of Biological Chemistry

1999, 274, 29951.

Patrica Soto

Is it possible to simulate the Is it possible to simulate the -sheet aggregate? -sheet aggregate? Molecular Dynamics simulations to investigate stability Molecular Dynamics simulations to investigate stability

of suprastructures of SIVwt peptide aggregates in DMSOof suprastructures of SIVwt peptide aggregates in DMSO

Frame at Tinitial

Distance between chain#1 and #30: ~12 nm

Simulation box with 30 parallel chains of SIVwt peptide in DMSO.Amount of particles: ~ 30000

The simulations show the spontaneous helical twisting of the The simulations show the spontaneous helical twisting of the protofibrilprotofibril

Patrica Soto

Spontaneous twisting…Spontaneous twisting…

t = 35 ns

t = 10 ns

t = 20 ns

t = 0 ns

t = 50 ns

•Parallel or antiparallel?

•Chirality

•Twisted ribbon as energetically more favorable geometry

Patrica Soto

SIVwt peptide spontaneously aggregates into stable SIVwt peptide spontaneously aggregates into stable clusters that exhibit high population of clusters that exhibit high population of -sheet secondary -sheet secondary

structurestructure

Is it possible to simulate the spontaneous aggregation Is it possible to simulate the spontaneous aggregation into ordered into ordered -sheet aggregates?-sheet aggregates?

Solvent: hexaneSolvent: hexane

t = 0nst = 2 ns

t = 20nst = 50ns

t = 75ns

t = 90ns

Patrica Soto

Is it possible to simulate the spontaneous aggregation Is it possible to simulate the spontaneous aggregation into ordered into ordered -sheet aggregates?-sheet aggregates?

Solvent: waterSolvent: water

SIVwt peptide spontaneously aggregates into stable SIVwt peptide spontaneously aggregates into stable clusters that exhibit high population of clusters that exhibit high population of -sheet secondary -sheet secondary

structurestructure

t = 0ns

t = 2ns

t = 35ns

t = 50ns

Patrica Soto