Adsorption of human serum albumin on the chrysotile surface: a molecular dynamics and spectroscopic investigation.

The human serum albumin (HSA) secondary structure modifications induced by the chrysotile surface have been investigated via computational molecular dynamics (MD) and experimental infrared spectroscopy (FTIR) on synthetic chrysotile nanocrystals coated with different amount of HSA. MD simulations, conducted by placing various albumin subdomains close to the fixed chrysotile surface, show an initial adsorption phase, accompanied by local rearrangements of the albumin motifs in contact with the chrysotile layer. Next, large-scale rearrangements follow with consequent secondary structure modifications. Gaussian curve fitting of the FTIR spectra obtained for HSA-coated synthetic chrysotile nanocrystals has allowed the quantification of HSA structural modifications as a function of the amount of protein adsorbed. The experimental results support the atomistic computer simulations providing a realistic description of the adsorption of plasma proteins onto chrysotile and unravelling a key step in the understanding of asbestos toxicity.

A molecular dynamics study of human serum albumin binding sites.

A 2.0 ns unrestrained Molecular Dynamics was used to elucidate the geometric and dynamic properties of the HSA binding sites. The structure is not stress affected and the rmsds calculated from the published crystallographic data are almost constant for all the simulation time, with an averaged value of 2.4A. The major variability is in the C-terminus region. The trajectory analysis of the IIA binding site put in evidence fast oscillations for the Cgamma@Leu203...Cgamma@Leu275 and Cgamma@Leu219...Cgamma@Leu260 distances, with fluctuations around 250 ps, 1000 ps and over for the first, while the second is smoothly increasing with the simulation time from 7 to 10A. These variations are consistent with a volume increase up to 20% confirmed by the inter-domain contacts analysis, in particular for the pair O@Pro148...Ogamma@Ser283, representing the change of distance between IB-h9 and IIA-h6, O@Glu149...Ogamma@Ser189 for sub-domains IB-h9/IIA-h1 and N@Val339...Odelta2@Asp447 sub-domains IIB-h9/IIIA-h1. These inter-domain motions confirm the flexibility of the unfatted HSA with possible binding site pre-formation.