Studies of drug binding to plasma proteins using a variant of equilibrium dialysis.

The plasma protein binding of three model compounds was investigated using a variant of equilibrium dialysis, denoted comparative equilibrium dialysis (CED), and the results were compared with those obtained with ultrafiltration (UF). In CED, the buffer that the plasma is dialysed against in traditional equilibrium dialysis is replaced by, for example, plasma from other species. The CED method has the advantage that the unbound concentration (C(u)) does not need to be measured, which can be difficult for drugs with extremely small unbound fractions.

A variable residue in the pore of Kv1 channels is critical for the high affinity of blockers from sea anemones and scorpions.

Animal toxins are associated with well defined selectivity profiles; however the molecular basis for this property is not understood. To address this issue we refined our previous three-dimensional models of the complex between the sea anemone toxin BgK and the S5-S6 region of Kv1.1 (Gilquin, B.

Modeling the structure of agitoxin in complex with the Shaker K+ channel: a computational approach based on experimental distance restraints extracted from thermodynamic mutant cycles.

Computational methods are used to determine the three-dimensional structure of the Agitoxin (AgTx2)-Shaker complex. In a first stage, a large number of models of the complex are generated using high temperature molecular dynamics, accounting for side chain flexibility with distance restraints deduced from thermodynamic analysis of double mutant cycles. Four plausible binding mode candidates are found using this procedure.