Study of the affinity between the protein kinase PKA and peptide substrates derived from kemptide using molecular dynamics simulations and MM/GBSA

Karel Mena-Ulecia, Ariela Vergara-Jaque, Horacio Poblete, William Tiznado, Julio Caballero

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

15 Citas (Scopus)

Resumen

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 (δδGE→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 (δδGE→TS) determined by the catalytic efficiency (kcat/KM) 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.

Idioma originalInglés
Número de artículo0109639
PublicaciónPLoS ONE
Volumen9
N.º10
DOI
EstadoPublicada - 2 oct 2014

Áreas temáticas de ASJC Scopus

  • Bioquímica, genética y biología molecular (todo)
  • Agricultura y biología (todo)
  • General

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