Peptide Conformations for a Microarray Surface-Tethered Epitope of the Tumor Suppressor p53

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• 作者：Jun Feng ; Ka-Yiu Wong ; Gillian C. Lynch ; Xiaolian Gao ; B. Montgomery Pettitt
• 刊名：Journal of Physical Chemistry B
• 出版年：2007
• 出版时间：December 13, 2007
• 年：2007
• 卷：111
• 期：49
• 页码：13797 - 13806
• 全文大小：813K
• 年卷期：v.111,no.49(December 13, 2007)
• ISSN：1520-5207

文摘

Peptides or proteins near surfaces exhibit different structural properties from those present in a homogeneoussolution, and these differences give rise to varied biological activity. Therefore, understanding the detailedmolecular structure of these molecules tethered to a surface is important for interpreting the performance ofthe various microarrays based on the activities of the immobilized peptides or proteins. We performed moleculardynamics simulations of a pentapeptide, RHSVV, an epitope of the tumor suppressor protein p53, tetheredvia a spacer on a functionalized silica surface and free in solution, to study their structural and conformationaldifferences. These calculations allowed analyses of the peptide-surface interactions, the sequence orientations,and the translational motions of the peptide on the surface to be performed. Conformational similarities arefound among dominant structures of the tethered and free peptide. In the peptide microarray simulations, thepeptide fluctuates between a parallel and tilted orientation driven in part by the hydrophobic interactionsbetween the nonpolar peptide residues and the methyl-terminated silica surface. The perpendicular movementof the peptide relative to the surface is also restricted due to the hydrophobic nature of the microarray surface.With regard to structures available for recognition and binding, we find that similar conformations to thosefound in solution are available to the peptide tethered to the surface, but with a shifted equilibrium constant.Comparisons with experimental results show important implications of this for peptide microarray designand assays.