Molecular Dynamics, Free Energy, and SPR Analyses of the Interactions between the SH2 Domain of Grb2 and ErbB Phosphotyrosyl Peptides

详细信息    查看全文

• 作者：Atsushi Suenaga ; Mariko Hatakeyama ; Mio Ichikawa ; Xiaomei Yu ; Noriyuki Futatsugi ; Tetsu Narumi ; Kazuhiko Fukui ; Takaho Terada ; Makoto Taiji ; Mikako Shirouzu ; Shigeyuki Yokoyama ; and Akihiko Konagaya
• 刊名：Biochemistry
• 出版年：2003
• 出版时间：May 13, 2003
• 年：2003
• 卷：42
• 期：18
• 页码：5195 - 5200
• 全文大小：301K
• 年卷期：v.42,no.18(May 13, 2003)
• ISSN：1520-4995

文摘

We studied the interactions between the SH2 domain of growth factor receptor binding protein2 (Grb2) and ErbB receptor-derived phosphotyrosyl peptides using molecular dynamics, free energycalculations, and surface plasmon resonance (SPR) analysis. Binding free energies for nine phosphotyrosylpeptides were calculated using the MM-PBSA continuum solvent method, and excellent qualitativeagreement with the SPR experimental data, with a correlation coefficient of 0.92, was obtained. Consistentwith previous experimental findings, phosphotyrosyl peptides with the consensus sequence pYXNX showedfavorable binding affinity for the Grb2. Unexpectedly, phosphotyrosyl peptides with the consensus sequencepYQQD, which had not shown any specific binding affinity for the Grb2 in earlier studies, also showedfavorable binding affinity for the Grb2 in our experimental and computational analyses. Component analysisof the calculated binding free energies revealed that van der Waals interaction between the Grb2 and thephosphotyrosyl peptide was the dominant factor for specificity and binding affinity. These results indicatethat current methods of estimating binding free energies are efficient for obtaining important informationabout protein-protein interactions, which are essential for the transmission of signals in cellular signalingpathways.