title: Unraveling the binding mechanism of polyoxyethylene sorbitan esters with bovine serum albumin: a novel theoretical model based on molecular dynamic simulations.
abstract: To gain a better understanding of the interactions governing the binding mechanism of proteins with non-ionic surfactants, the association processes of Tween 20 and Tween 80 with the bovine serum albumin (BSA) protein were investigated using molecular dynamics (MD) simulations. Protein:surfactant molar ratios were chosen according to the critical micelle concentration (CMC) of each surfactant in the presence of BSA. It was found that both the hydrophilic and the hydrophobic groups of the BSA equally contribute to the surface area of interaction with the non-ionic surfactants. A novel theoretical model for the interactions between BSA and these surfactants at the atomic level is proposed, where both surfactants bind to non-specific domains of the BSA three-dimensional structure mainly through their polyoxyethylene groups, by hydrogen bonds and van der Waals interactions. This is well supported by the strong electrostatic and van der Waals interaction energies obtained in the calculations involving surfactant polyoxyethylene groups and different protein regions. The results obtained from the MD simulations suggest that the formation of surfactant clusters over the BSA structure, due to further cooperative self-assembly of Tween molecules, could increase the protein conformational stability. These results extend the current knowledge on molecular interactions between globular proteins and non-ionic surfactants, and contribute to the fine-tuning design of protein formulations using polysorbates as excipients for minimizing the undesirable effects of protein adsorption and aggregation.
authors.affiliation: Laboratorio de Biología Computacional, Centro de Estudios de Proteína (CEP), Facultad de Biología, Universidad de La Habana, Habana 10400, Cuba.
authors.forename: Karelia H
authors.initials: KH
authors.lastname: Delgado-Magnero
authors.affiliation: Laboratorio de Biología Computacional, Centro de Estudios de Proteína (CEP), Facultad de Biología, Universidad de La Habana, Habana 10400, Cuba.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Valiente
authors.affiliation: Departamento de Radioquímica, Instituto Superior de Tecnologías y Ciencias Aplicadas (InSTEC), P.O. Box 6163, La Habana 10400, Cuba.
authors.forename: Miriam
authors.initials: M
authors.lastname: Ruiz-Peña
authors.affiliation: Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro 22453-900, Brazil.
authors.forename: Aurora
authors.initials: A
authors.lastname: Pérez-Gramatges
authors.affiliation: Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, Madrid E-28029, Spain. Electronic address: tpons@cnio.es.
authors.forename: Tirso
authors.initials: T
authors.lastname: Pons
mesh_terms: D000327:Adsorption; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D004952:Esters / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011092:Polyethylene Glycols / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D004952:Esters; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols
keywords: BSA; Molecular dynamics simulations; Non-ionic surfactants; Polysorbates; Tween