title: Study of the affinity between the protein kinase PKA and peptide substrates derived from kemptide using molecular dynamics simulations and MM/GBSA.
abstract: We have carried out a protocol in computational biochemistry including molecular dynamics (MD) simulations and MM/GBSA free energy calculations on the complex between the protein kinase A (PKA) and the specific peptide substrate Kemptide (LRRASLG). We made the same calculations on other PKA complexes that contain Kemptide derivatives (with mutations of the arginines, and with deletions of N and C-terminal amino acids). We predicted shifts in the free energy changes from the free PKA to PKA-substrate complex (ΔΔG(E→ES)) when Kemptide structure is modified (we consider that the calculated shifts correlate with the experimental shifts of the free energy changes from the free PKA to the transition states (ΔΔG(E→TS)) determined by the catalytic efficiency (k(cat)/K(M)) changes). Our results demonstrate that it is possible to predict the kinetic properties of protein kinases using simple computational biochemistry methods. As an additional benefit, these methods give detailed molecular information that permit the analysis of the atomic forces that contribute to the affinity between protein kinases and their substrates.
authors.affiliation: Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago de Chile, Chile.
authors.forename: Karel
authors.initials: K
authors.lastname: Mena-Ulecia
authors.affiliation: Centro de Bioinformática y Simulación Molecular, Facultad de Ingeniería, Universidad de Talca, Talca, Chile.
authors.forename: Ariela
authors.initials: A
authors.lastname: Vergara-Jaque
authors.affiliation: Centro de Bioinformática y Simulación Molecular, Facultad de Ingeniería, Universidad de Talca, Talca, Chile.
authors.forename: Horacio
authors.initials: H
authors.lastname: Poblete
authors.affiliation: Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago de Chile, Chile.
authors.forename: William
authors.initials: W
authors.lastname: Tiznado
authors.affiliation: Centro de Bioinformática y Simulación Molecular, Facultad de Ingeniería, Universidad de Talca, Talca, Chile.
authors.forename: Julio
authors.initials: J
authors.lastname: Caballero
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D009842:Oligopeptides; C037642:kemptide; D017868:Cyclic AMP-Dependent Protein Kinases