Atomistic Simulations of PAP248-286 Peptide Oligomerization

Amyloid fibrils, dubbed SEVI (semen-derived enhancer of virus infection), contribute to the spread of HIV infection. The main components of SEVI are the fragments of prostatic acid phosphatase (PAP): PAP248-286 and PAP85-120. SEVI captures the viral particles and further stimulates their attachment to the target cells, thereby boosting viral fusion and infec-tion. To study the oligomers of SEVI-forming peptides, we used molecular modeling, which is a powerful tool that has been applied in a great variety of studies on SEVI, and an advanced accelerated sampling method of metadynamics. Based on the obtained molecular dynamics data, it was shown that PAP248-286 has a horseshoe shape with bends in the regions of amino acid residues A274 and N269 in the dimeric state. It was suggested that the horseshoe shape might lead in the fibrillation process to the steric zipper model formation, which is typical of amyloids. It was confirmed that the process of fibril formation of PAP248-286 starts with a pairwise parallel arrangement of the peptide helical regions.