Cyclodextrins (CDs) are widely used in the pharmaceutical industry as transporters of lipophilic drugs due to their amphiphilic nature. The detailed study of the molecular interactions of drug complexes with CDs is very important in designing the best formulation for the transportation of lipophilic drugs. The drug: CD binding should be strong enough so that the complex is stable in the aquatic environment of the extracellular fluids, but also not very strong in order for the drug to be capable for being released in the proximity of the target receptor. In a recent study, we investigated the ΔG of binding between the commercially available, nontoxic 2-hydroxypropyl-β-cyclodextrin (2-HP-B-CD) and the antihypertensive drug candesartan cilexetil (CC), with the use of steered (or biased) molecular dynamics (sMD) and umbrella sampling method. This chapter describes comprehensively how to perform sMD and umbrella sampling in order to calculate the ΔGbinding of CC to the 2-HP-B-CD.
Keywords: Biased MD; Candesartan; Drug transporter; Hypertension; Lipophilicity; Steered MD; Umbrella sampling; ΔGbinding.