title: Modeling conformational transitions in kinases by molecular dynamics simulations: achievements, difficulties, and open challenges.
abstract: Protein kinases work because their flexibility allows to continuously switch from inactive to active form. Despite the large number of structures experimentally determined in such states, the mechanism of their conformational transitions as well as the transition pathways are not easily to capture. In this regard, computational methods can help to shed light on such an issue. However, due to the intrinsic sampling limitations, much efforts have been done to model in a realistic way the conformational changes occurring in protein kinases. In this review we will address the principal biological achievements and structural aspects in studying kinases conformational transitions and will focus on the main challenges related to computational approaches such as molecular modeling and MD simulations.
authors.affiliation: CINECA Rome, Italy ; Dipartimento di Chimica, Sapienza University of Rome Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: D'Abramo
authors.affiliation: Dipartimento di Scienze e Tecnologie Chimiche, Università di Roma "Tor Vergata," Rome, Italy.
authors.forename: Neva
authors.initials: N
authors.lastname: Besker
authors.affiliation: CINECA Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Chillemi
authors.affiliation: CINECA Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Grottesi
keywords: computational modeling; conformational pathways; conformational transitions; kinases; molecular dynamics