10 research outputs found
The Dynamics of Ca2+ Ions within the Solvation Shell of Calbindin D9k
The encounter of a Ca2+ ion with a protein and its subsequent
binding to specific binding sites is an intricate process that cannot be fully
elucidated from experimental observations. We have applied Molecular Dynamics to
study this process with atomistic details, using Calbindin D9k (CaB) as a model
protein. The simulations show that in most of the time the Ca2+
ion spends within the Debye radius of CaB, it is being detained at the 1st and
2nd solvation shells. While being detained near the protein, the diffusion
coefficient of the ion is significantly reduced. However, due to the relatively
long period of detainment, the ion can scan an appreciable surface of the
protein. The enhanced propagation of the ion on the surface has a functional
role: significantly increasing the ability of the ion to scan the protein's
surface before being dispersed to the bulk. The contribution of this mechanism
to Ca2+ binding becomes significant at low ion concentrations,
where the intervals between successive encounters with the protein are getting
longer. The efficiency of the surface diffusion is affected by the distribution
of charges on the protein's surface. Comparison of the Ca2+
binding dynamics in CaB and its E60D mutant reveals that in the wild type (WT)
protein the carboxylate of E60 function as a preferred landing-site for the
Ca2+ arriving from the bulk, followed by delivering it to
the final binding site. Replacement of the glutamate by aspartate significantly
reduced the ability to transfer Ca2+ ions from D60 to the final
binding site, explaining the observed decrement in the affinity of the mutated
protein to Ca2+
La Sédation en imagerie pédiatrique (revue de la littérature et résultats d'une étude prospective de 101 cas de sédations par chlorpromazine intraveineuse chez des enfants de moins de 6 ans)
LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF