Data for: Caspase-Based Fusion Protein Technology: Substrate Cleavability Described by Computational Modeling and Simulation

Description

Abstract (English)

The Caspase-based fusion protein technology (CASPON) allows for universal cleavage of fusion tags from proteins of interest, to reconstitute the native N-terminus. While the CASPON enzyme has been optimized to be promiscuous against a diversity of N-terminal peptides, the cleavage efficacy for larger proteins can be surprisingly low. We develop an efficient means to rationalize and predict the cleavage efficiency based on a structural representation of the intrinsically disordered N-terminal peptides, and their putative interactions with the CASPON enzyme. The number of favourably interacting N-terminal conformations shows a very good agreement with the experimentally observed cleavage efficiency, in agreement with a conformational selection model. The method relies on computationally cheap molecular dynamics simulations to efficiently generate a diverse collection of N-terminal conformation, followed by a simple fitting procedure into the CASPON enzyme. It can be readily used to assess CASPON cleavability a priori.