Melittin Aggregation in Aqueous Solutions: Insight from Molecular Dynamics Simulations.
J Phys Chem B
; 119(33): 10390-8, 2015 Aug 20.
Article
em En
| MEDLINE
| ID: mdl-26208115
ABSTRACT
Melittin is a natural peptide that aggregates in aqueous solutions with paradigmatic monomer-to-tetramer and coil-to-helix transitions. Since little is known about the molecular mechanisms of melittin aggregation in solution, we simulated its self-aggregation process under various conditions. After confirming the stability of a melittin tetramer in solution, we observedfor the first time in atomistic detailthat four separated melittin monomers aggregate into a tetramer. Our simulated dependence of melittin aggregation on peptide concentration, temperature, and ionic strength is in good agreement with prior experiments. We propose that melittin mainly self-aggregates via a mechanism involving the sequential addition of monomers, which is supported by both qualitative and quantitative evidence obtained from unbiased and metadynamics simulations. Moreover, by combining computer simulations and a theory of the electrical double layer, we provide evidence to suggest why melittin aggregation in solution likely stops at the tetramer, rather than forming higher-order oligomers. Overall, our study not only explains prior experimental results at the molecular level but also provides quantitative mechanistic information that may guide the engineering of melittin for higher efficacy and safety.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Água
/
Simulação de Dinâmica Molecular
/
Agregados Proteicos
/
Meliteno
Tipo de estudo:
Qualitative_research
Idioma:
En
Revista:
J Phys Chem B
Assunto da revista:
QUIMICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos