A molecular dynamics study of human serum albumin binding sites

Abstract

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 2.4Å. The major variability is in the C-terminus region. The trajectory analysis of the IIA binding site put in evidence fast oscillations for the Cγ@Leu203···Cγ@Leu275 and Cγ@Leu219···Cγ@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 10Å. 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···Oγ@Ser283, representing the change of distance between IB-h9 and IIA-h6, O@Glu149···Oγ@Ser189 for sub-domains IB-h9/IIA-h1 and N@Val339···Oδ2@Asp447 sub-domains IIB-h9/IIIA-h1. These inter-domain motions confirm the flexibility of the unfatted HSA with possible binding site pre-formation.