Quantitative Assessment of Protein Interaction with Methyl-Lysine Analogues by Hybrid Computational and Experimental Approaches

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• 作者：Daniel Seeliger ; Szabolcs Soeroes ; Rebecca Klingberg ; Dirk Schwarzer ; Helmut Grubm眉ller ; Wolfgang Fischle
• 刊名：ACS Chemical Biology
• 出版年：2012
• 出版时间：January 20, 2012
• 年：2012
• 卷：7
• 期：1
• 页码：150-154
• 全文大小：230K
• 年卷期：v.7,no.1(January 20, 2012)
• ISSN：1554-8937

文摘

In cases where binding ligands of proteins are not easily available, structural analogues are often used. For example, in the analysis of proteins recognizing different methyl-lysine residues in histones, methyl-lysine analogues based on methyl-amino-alkylated cysteine residues have been introduced. Whether these are close enough to justify quantitative interpretation of binding experiments is however questionable. To systematically address this issue, we developed, applied, and assessed a hybrid computational/experimental approach that extracts the binding free energy difference between the native ligand (methyl-lysine) and the analogue (methyl-amino-alkylated cysteine) from a thermodynamic cycle. Our results indicate that measured and calculated binding differences are in very good agreement and therefore allow the correction of measured affinities of the analogues. We suggest that quantitative binding parameters for defined ligands in general can be derived by this method with remarkable accuracy.