Biological signaling pathways and protein transport systems ensure that fundamental processes of the cell, such as localization of proteins, DNA replication and protein synthesis are carried out with exquisite accuracy and efficiency. A representative system of these processes is the signal recognition particle (SRP), which recognizes proteins via their signal sequences for the co-translational protein-targeting pathway. A careful analysis of peptide binding to two key SRP conformations by free energy perturbation is performed to identify the key features of the binding event. Construction of a thermodynamic cycle is done to compare the relative stabilization of the each conformation conferred by signal sequence binding. The local effects of peptide binding are then linked with the large domain rearrangements seen in the SRP crystal structures through long timescale simulations.

Molecular simulation of SRP binding in co-translational protein targeting: Understanding the origin of high fidelity in biomolecular pathways

243rd National Meeting (2012)

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