SPEADI: Accelerated Analysis of IDP-Ion Interactions from MD-Trajectories

SIMPLE SUMMARY: Intrinsically Disordered Proteins (IDPs) are particularly sensitive to changes in chemical environmental conditions. Changes in this environment lead to alterations of their normal functions. We introduce the concept of a Time-Resolved Radial Distribution Function (TRRDF). TRRDFs are able to characterize the local environment dynamics in simulations around dynamically changing IDPs. TRRDFs are implemented and available in our open-source Python package SPEADI. We use SPEADI to characterize the dynamic distribution of ions around two IDPs Alpha-Synuclein (AS) and Humanin (HN) from Molecular Dynamics (MD) simulations. We analyze and explore the local ion–residue interactions that play an important role in the structures and behaviors of IDPs. ABSTRACT: The disordered nature of Intrinsically Disordered Proteins (IDPs) makes their structural ensembles particularly susceptible to changes in chemical environmental conditions, often leading to an alteration of their normal functions. A Radial Distribution Function (RDF) is considered a standard method for characterizing the chemical environment surrounding particles during atomistic simulations, commonly averaged over an entire or part of a trajectory. Given their high structural variability, such averaged information might not be reliable for IDPs. We introduce the Time-Resolved Radial Distribution Function (TRRDF), implemented in our open-source Python package SPEADI, which is able to characterize dynamic environments around IDPs. We use SPEADI to characterize the dynamic distribution of ions around the IDPs Alpha-Synuclein (AS) and Humanin (HN) from Molecular Dynamics (MD) simulations, and some of their selected mutants, showing that local ion–residue interactions play an important role in the structures and behaviors of IDPs.