Molecular dynamics simulation and docking studies on the binding properties of several anticancer drugs to human serum albumin

Disposition and transportation of anticancer drugs by human serum albumin (HSA) affects their bioavailability, distribution and elimination. In this study, the interaction of a set of anticancer drugs with HSA was investigated by molecular dynamics and molecular docking simulations. The drugs' activities were analyzed according to their docking scores, binding sites and structural descriptors. The results displayed the ability of cavity 1, located in the cleft between domains I and III, to potentiate as the principal binding site of all tested drugs. This cavity provides a large space without any effective steric hindrance and induces the stability of the drugs in their binding sites by short and long ranged interactions with the accessible residues. Yet, specific structural features may lead some drug configurations to advance stronger interactions with cavities other than cavity 1. Also, the small volume and position of some cavities i.e. cavities 3, 5-10 involve penetration, small molecular volume and specific geometry which consequently force most drugs out of the corresponding binding sites.  Therefore, the steric factor seems to play the most important role in the transportation of drugs by HSA.