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Previously reported [http://arxiv.org/abs/1506.06433] reprogramming ofsubstrate specificity of H3K4Me3 epigenetic marks reading PHD domain of BPTFprotein illustrates therapeutic potential of a new class of non-inhibitor smallorganic compounds - variators. Here we address the question aboutreproducibility of rational design of variators by reprogramming of the secondepigenetic marks reading domain of BPTF protein - bromodomain. Bromodomain ofBPTF binds to epigenetic marks in form of acetylated lysine of histone H4(H4K12Ac, H4K16Ac and H4K20Ac), which physicochemical properties and bindingmode differs considerably from those of methylated H3K4 marks. Thus, detaileddescription of computational approach for reprogramming of bromodomainsubstrate specificity illustrates both general and target specific attributesof computer aided variators design.

New class of compounds - variators - are reprogramming substrate  specificity of H4K12Ac, H4K16Ac and H4K20Ac epigenetic marks reading  bromodomain of BPTF protein