The binding of apo and glucose-bound human serum albumins to a free graphene sheet in aqueous environment: Simulation studies.

Human serum albumin (HSA) is a blood protein serving as a carrier for a wide range of drugs and nutrients. A level of glycated HSA (GHSA) is used as a diabetes biomarker. A graphene-based aptasensor is one of potential techniques to detect GHSA. Not only the interactions of albumin and aptamer, but the albumin-graphene (GRA) binding mechanism are also crucial for developing a diabetes aptasensor. In this work, Molecular Dynamics simulations (MD) were employed to explore the binding of GRA to both GHSA and HSA. The GRA binding from the back and front sides of an albumin are fast and spontaneous. The multiple GRA binding sites are identified. GRA causes more denaturation of helical characteristics in GHSA (∼12% reduction of helical structure). Both back and front GRA adhesions generate comparable degrees of helical unfolding. Importantly, the presence of bound GRA induces the release of glucose from drug sites implying the loss of ligand-binding affinity. This loss of drug site activity is independent on the GRA binding positions because all bound positions lead to the exit of sugars. The GRA binding deconstructs not only secondary structure, but also albumin function. Apparently, GRA is a non-biocompatible material for albumin. To construct a potential graphene-based aptasensor to detect GHSA, it is necessary to be certain that no free GRA surface is available because a bare GRA can bind and denature both HSA and GHSA which can cause misleading data.