Molecular Dynamics Simulation of Dendrimers: Structural Formation and Internal Charge Distribution

2004 ◽  
Author(s):  
Takamichi Terao
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Charge Distribution ◽  
Dynamics Simulation ◽  
Structural Formation ◽  
Internal Charge

scholarly journals Charge-mediated influence of the antibody variable domain on FcRn-dependent pharmacokinetics

2015 ◽  
Vol 112 (19) ◽  
pp. 5997-6002 ◽  
Author(s):  
Angela Schoch ◽  
Hubert Kettenberger ◽  
Olaf Mundigl ◽  
Gerhard Winter ◽  
Julia Engert ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Charge Distribution ◽  
Underlying Mechanism ◽  
Antibody Engineering ◽  
Dynamics Simulation ◽  
Antigen Binding ◽  
Igg Antibodies ◽  
Neonatal Fc Receptor

Here, we investigated the influence of the variable fragment (Fv) of IgG antibodies on the binding to the neonatal Fc receptor (FcRn) as well as on FcRn-dependent pharmacokinetics (PK). FcRn plays a key role in IgG homeostasis, and specific manipulation in the crystallizable fragment (Fc) is known to affect FcRn-dependent PK. Although the influence of the antigen-binding fragment (Fab) on FcRn interactions has been reported, the underlying mechanism is hitherto only poorly understood. Therefore, we analyzed the two IgG1 antibodies, briakinumab and ustekinumab, that have similar Fc parts but different terminal half-lives in human and systematically engineered variants of them with cross-over exchanges and varied charge distribution. Using FcRn affinity chromatography, molecular dynamics simulation, and in vivo PK studies in human FcRn transgenic mice, we provide evidence that the charge distribution on the Fv domain is involved in excessive FcRn binding. This excessive binding prevents efficient FcRn–IgG dissociation at physiological pH, thereby reducing FcRn-dependent terminal half-lives. Furthermore, we observed a linear correlation between FcRn column retention times of the antibody variants and the terminal half-lives in vivo. Taken together, our study contributes to a better understanding of the FcRn–IgG interaction, and it could also provide profound potential in FcRn-dependent antibody engineering of the variable Fab region.

scholarly journals Dynamic behaviour of the silica-water-bio electrical double layer in the presence of a divalent electrolyte

2017 ◽  
Vol 19 (4) ◽  
pp. 2687-2701 ◽  
Author(s):  
B. M. Lowe ◽  
Y. Maekawa ◽  
Y. Shibuta ◽  
T. Sakata ◽  
C.-K. Skylaris ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Charge Distribution ◽  
Double Layer ◽  
Electrical Double Layer ◽  
Electric Double Layer ◽  
Dynamic Behaviour ◽  
Dynamics Simulation ◽  
Mixed Electrolyte

Molecular dynamics simulation of the electric double layer at the silica-water-bio interface in mixed electrolyte. Water orientation and charge distribution showed a significant effect on the electrostatics at the interface.

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