title: Exploring the Unfolding Pathway of Maltose Binding Proteins: An Integrated Computational Approach.
abstract: Recent single-molecule force spectroscopy experiments on the Maltose Binding Proteins (MBPs) identified four stable structural units, termed unfoldons, that resist mechanical stress and determine the intermediates of the unfolding pathway. In this work, we analyze the topological origin and the dynamical role of the unfoldons using an integrated approach which combines a graph-theoretical analysis of the interaction network of the MBP native-state with steered molecular dynamics simulations. The topological analysis of the native state, while revealing the structural nature of the unfoldons, provides a framework to interpret the MBP mechanical unfolding pathway. Indeed, the experimental pathway can be effectively predicted by means of molecular dynamics simulations with a simple topology-based and low-resolution model of the MBP. The results obtained from the coarse-grained approach are confirmed and further refined by all-atom molecular dynamics.
authors.affiliation: Dipartimento di Fisica, Università di Roma "Sapienza" , I-00185, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Guardiani
authors.affiliation: Dipartimento di Fisica, Università di Roma "Sapienza" , I-00185, Rome, Italy.
authors.forename: Daniele Di
authors.initials: DD
authors.lastname: Marino
authors.affiliation: Dipartimento di Fisica, Università di Roma "Sapienza" , I-00185, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Tramontano
authors.affiliation: Center for Life Nano Science, Istituto Italiano di Tecnologia (IIT) , I-00185, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Chinappi
authors.affiliation: CNR-Istituto dei Sistemi Complessi (ISC) , Via dei Taurini 19, I-00185, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Cecconi