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Folding Simulations

Sibylla’s key differentiator is its protein folding computational platform, which enables the reconstruction of the complex series of conformational rearrangements underlying the process of protein folding at an all-atom level of detail.

In living cells, the process of protein folding takes milliseconds to minutes. With standard molecular dynamics techniques it’s impossible to reach such timescales for biologically-relevant proteins, even by employing the most powerful existing special-purpose supercomputer. In contrast, our algorithms can accelerate the exploration of proteins’ conformational landscape, enabling us to characterize their folding pathways and identify relevant intermediate states.

The strength of our predictions relies on the inclusion in our simulations of key features of protein folding as it occurs in living cells. Indeed, the folding of most proteins occurs while they are being synthesized by the ribosome, which thus considerably shapes their folding pathway. Our co-translational and co-translocational technologies allow us to capture the important contribution of the ribosome and associated translocation machinery to the folding process. The following movie shows more details on the working of this method.

Co-translational folding can be applied to understand the folding pathway of proteins that fold in the cytosol. The folding of proteins that belong to the secretory pathway can be studied with our co-translocational simulations, where the protein is translocated from the cytosol to the endoplasmic reticulum lumen through the translocation channel of the Sec61 Complex.