Quantitative assessment of protein interaction with methyl-lysine analogues by hybrid computational and experimental approaches.

ABSTRACT: 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 agree

SUBMITTER: Seeliger D 

PROVIDER: S-EPMC3265130 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature