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Abstract

Experimental protein structures provide spatial information at the atomic level. A further dimension, time, is supplemented by molecular dynamics. Since the pioneering work on the 58-residue inhibitor of bovine pancreatic trypsin in the group of Martin Karplus in the seventies, molecular dynamics simulations have shown that the intrinsic flexibility of proteins is essential for their function. Here, we review simulation studies of bromodomains. These protein modules are involved in the recognition of acetylated lysine side chains, a post-translational modification frequently observed in histone tails. The molecular dynamics simulations have unmasked: (i) the large plasticity of the loops lining the acetyl-lysine binding site (coupled to its self-occlusion), and (ii) multiple binding modes of acetyl-lysine. These simulation results suggest that recognition of histone tails by bromodomains is modulated by their intrinsic flexibility, and further corroborate the utility of molecular dynamics in understanding (macro)molecular recognition.

Year of Publication
2014
Journal
Israel Journal of Chemistry
Volume
54
Issue
8-9
Number of Pages
1084–1092
Date Published
Aug 2014
Type of Article
Review Article
ISSN Number
1869-5868
URL
http://dx.doi.org/10.1002/ijch.201400009
DOI
10.1002/ijch.201400009
Alternate Journal
Isr. J. Chem.
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