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Molecular simulation of the binding of nerve growth factor peptide mimics to the receptor tyrosine kinase A
被引:21
作者:
Berrera, Marco
Cattaneo, Antonino
Carloni, Paolo
[1
]
机构:
[1] Scuola Int Super Studi Avanzati, Trieste, Italy
[2] Democritos Modeling Ctr Res Atomist Simulat, Ist Nazl Fis Materia, Trieste, Italy
[3] European Brain Res Inst, Rome, Italy
关键词:
D O I:
10.1529/biophysj.106.083519
中图分类号:
Q6 [生物物理学];
学科分类号:
071011 ;
摘要:
Nerve growth factor (NGF) mimics play an important role for therapies that target the receptor tyrosine kinase A (trkA). The N-terminal fragment of the NGF (N-term@NGF) was previously demonstrated to be an important determinant for affinity and specificity in the binding to trkA. Here we use a variety of computational tools (contact surface analysis and free energy predictions) to identify residues playing a key role for the binding to the receptor. Molecular dynamics simulations are then used to investigate the stability of complexes between trkA and peptides mimicking N-term@NGF. Steered molecular dynamics calculations are finally performed to investigate the process of detaching the peptide from the receptor. Three disruptive events are observed, the first involving the breaking of all intermolecular interactions except two salt bridges, which break subsequently.
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页码:2063 / 2071
页数:9
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