Molecular dynamics of protein kinase-inhibitor complexes: a valid structural information

Current Pharmaceutical Design
Julio Caballero, Jans H Alzate-Morales

Abstract

Protein kinases (PKs) are key components of protein phosphorylation based signaling networks in eukaryotic cells. They have been identified as being implicated in many diseases. High-resolution X-ray crystallographic data exist for many PKs and, in many cases, these structures are co-complexed with inhibitors. Although this valuable information confirms the precise structure of PKs and their complexes, it ignores the dynamic movements of the structures which are relevant to explain the affinities and selectivity of the ligands, to characterize the thermodynamics of the solvated complexes, and to derive predictive models. Atomistic molecular dynamics (MD) simulations present a convenient way to study PK-inhibitor complexes and have been increasingly used in recent years in structure-based drug design. MD is a very useful computational method and a great counterpart for experimentalists, which helps them to derive important additional molecular information. That enables them to follow and understand structure and dynamics of protein-ligand systems with extreme molecular detail on scales where motion of individual atoms can be tracked. MD can be used to sample dynamic molecular processes, and can be complemented with more advanced...Continue Reading

Citations

Jan 18, 2013·PloS One·Angela StrambiMario Chiariello
Jan 1, 2014·Molecular Simulation·Priyanka Prakash, Alemayehu A Gorfe
Dec 14, 2016·Journal of Chemical Information and Modeling·Rajni K SharmaKelly Chibale
Dec 23, 2017·Toxins·Paola G OjedaWendy González
Oct 7, 2016·The Open Medicinal Chemistry Journal·David Ramírez
Feb 26, 2019·Scientific Reports·Jose Luis Dominguez, Bernhard Knapp
Jan 24, 2020·Frontiers in Chemistry·Zarko GagicKatarina Nikolic
Oct 2, 2013·Molecular Diversity·Luisa Quesada-Romero, Julio Caballero
Dec 2, 2014·Journal of Medicinal Chemistry·Paul CzodrowskiDjordje Musil
Feb 16, 2013·Journal of Chemical Information and Modeling·Marlene Espinoza-MoragaKelly Chibale

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