Unraveling the binding mechanism of polyoxyethylene sorbitan esters with bovine serum albumin: A novel theoretical model based on molecular dynamic simulations

被引:22
作者
Delgado-Magnero, Karelia H. [1 ]
Valiente, Pedro A. [1 ]
Ruiz-Pena, Miriam [2 ]
Perez-Gramatges, Aurora [3 ]
Pons, Tirso [4 ]
机构
[1] Univ La Habana, Fac Biol, Ctr Estudios Prot, Lab Biol Computac, Havana 10400, Cuba
[2] Inst Super Tecnol & Ciencias Aplicadas InSTEC, Dept Radioquim, Havana 10400, Cuba
[3] Pontificia Univ Catolica Rio de Janeiro, Dept Quim, BR-22453900 Rio De Janeiro, Brazil
[4] Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomp Programme, E-28029 Madrid, Spain
关键词
Non-ionic surfactants; BSA; Tween; Polysorbates; Molecular dynamics simulations; PARTICLE MESH EWALD; RECONSTITUTION MEDIUM; POLYSORBATE; 20; PROTEIN; STABILITY; DENATURATION; FORMULATIONS; AGGREGATION; SURFACTANTS; EFFICIENT;
D O I
10.1016/j.colsurfb.2013.11.018
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
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. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:720 / 726
页数:7
相关论文
共 55 条
[1]   Calorimetric and structural investigation of the interaction of lysozyme and bovine serum albumin with poly(ethylene oxide) and its copolymers [J].
Almeida, NL ;
Oliveira, CLP ;
Torriani, IL ;
Loh, W .
COLLOIDS AND SURFACES B-BIOINTERFACES, 2004, 38 (1-2) :67-76
[2]   ESSENTIAL DYNAMICS OF PROTEINS [J].
AMADEI, A ;
LINSSEN, ABM ;
BERENDSEN, HJC .
PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1993, 17 (04) :412-425
[3]   An efficient method for sampling the essential subspace of proteins [J].
Amadei, A ;
Linssen, ABM ;
deGroot, BL ;
vanAalten, DMF ;
Berendsen, HJC .
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 1996, 13 (04) :615-625
[4]  
[Anonymous], 1999, PHYS DESK REFERENCE
[5]  
[Anonymous], 2012, AMBER 12
[6]  
Arakawa T, 2000, J PHARM SCI, V89, P646, DOI 10.1002/(SICI)1520-6017(200005)89:5<646::AID-JPS10>3.3.CO
[7]  
2-A
[8]  
Ayorinde FO, 2000, RAPID COMMUN MASS SP, V14, P2116, DOI 10.1002/1097-0231(20001130)14:22<2116::AID-RCM142>3.0.CO
[9]  
2-1
[10]   STABILITY OF PROTEIN FORMULATIONS - INVESTIGATION OF SURFACTANT EFFECTS BY A NOVEL EPR SPECTROSCOPIC TECHNIQUE [J].
BAM, NB ;
RANDOLPH, TW ;
CLELAND, JL .
PHARMACEUTICAL RESEARCH, 1995, 12 (01) :2-11