1. One 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-IR 1 and ThioflavinT fluorescence 2  sheet aggregates depending on peptide concentration. 1. Martin, I. et al. Journal of Virology, 1994, 68, 1139 2. Cladera, J. et al. Journal of Biological Chemistry 1999, 274, 29951. Patrica Soto

2. Is it possible to simulate the  -sheet aggregate? Molecular Dynamics simulations to investigate stability of suprastructures of SIVwt peptide aggregates in DMSO Frame at T initial 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 protofibril Patrica Soto

3. 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

4. SIVwt peptide spontaneously aggregates into stable clusters that exhibit high population of  -sheet secondary structure Is it possible to simulate the spontaneous aggregation into ordered  -sheet aggregates? Solvent: hexane t = 0ns t = 2 ns t = 20ns t = 50ns t = 75ns t = 90ns Patrica Soto

5. Is it possible to simulate the spontaneous aggregation into ordered  -sheet aggregates? Solvent: water SIVwt peptide spontaneously aggregates into stable clusters that exhibit high population of  -sheet secondary structure t = 0ns t = 2ns t = 35ns t = 50ns Patrica Soto