分子动力学研究抗体SPE7与抗原Alizarin red的相互作用机制

Insight into interaction mechanism of antibody SPE7 with antigen alizarin red by molecular dynamics simulations

摘要:

研究抗原与抗体的相互作用机制在治疗与抗体相关疾病药物的研发中起到重要作用. 采用分子动力学模拟和MM-PBSA(molecular mechanics-Poisson Boltzmann surface area)以及溶解相互作用能SIE(solvated interaction energy)方法研究了抗原Alizarin red(AZN)与抗体SPE7的结合模式. 研究结果证明范德华作用主导了抗原AZN与抗体SPE7的相互作用. 基于残基能量分解的计算表明抗原AZN能与残基H-W35、H-Y105、L-Y34和L-W93产生较强的相互作用, 此结果表明AZN与SPE7分离残基间的π-π相互作用驱动了AZN与SPE7的结合. 期望这个研究能为治疗与抗体相关疾病药物的研发提供重要的理论指导.

Abstract:

The interaction mechanism of antigens with antibodies plays an important role in development of drugs curing diseases related with antibodies. In this work, molecular dynamics simulations combined with molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) method and solvated interaction energy (SIE) were carried out to study the binding mode of antigen Alizarin red (AZN) to antibody SPE7. The results show that van der Waals interaction is a main force to control the interaction of AZN with SPE7. The calculations from residue-based free energy decomposition indicates that the π-π interaction of AZN with separate residues in SPE7 drives the binding of AZN to SPE7. More detailed, AZN produces strong interactions with the residues H-W35、H-Y105、L-Y34 and L-W93 in SPE7. We expect that this work can provide theoretical guidance for the development of drugs targeting the interactions of antigens with antibodies.