Premium
Molecular Dynamics Simulations of Bromodomains Reveal Binding‐Site Flexibility and Multiple Binding Modes of the Natural Ligand Acetyl‐Lysine
Author(s) -
Spiliotopoulos Dimitrios,
Caflisch Amedeo
Publication year - 2014
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1002/ijch.201400009
Subject(s) - chemistry , bromodomain , molecular dynamics , acetylation , lysine , histone , nucleosome , molecular recognition , binding site , biophysics , computational biology , stereochemistry , amino acid , biochemistry , computational chemistry , molecule , dna , biology , organic chemistry , gene
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.