  Previously reported [http://arxiv.org/abs/1506.06433] reprogramming of
substrate specificity of H3K4Me3 epigenetic marks reading PHD domain of BPTF
protein illustrates therapeutic potential of a new class of non-inhibitor small
organic compounds - variators. Here we address the question about
reproducibility of rational design of variators by reprogramming of the second
epigenetic marks reading domain of BPTF protein - bromodomain. Bromodomain of
BPTF binds to epigenetic marks in form of acetylated lysine of histone H4
(H4K12Ac, H4K16Ac and H4K20Ac), which physicochemical properties and binding
mode differs considerably from those of methylated H3K4 marks. Thus, detailed
description of computational approach for reprogramming of bromodomain
substrate specificity illustrates both general and target specific attributes
of computer aided variators design.
