Fig. 4: Hairpin conformations facilitate the access of the peptide into the binding cleft of SETD2. | Communications Chemistry

Fig. 4: Hairpin conformations facilitate the access of the peptide into the binding cleft of SETD2.

From: Mechanistic basis of the increased methylation activity of the SETD2 protein lysine methyltransferase towards a designed super-substrate peptide

Fig. 4

a sMD simulation of H3K36 and ssK36 driven by a distant dependent external force of 0.5 kJ/(mol × Å2) between the Nε-atom of K36 and the methyl group C-atom of SAM. Shown is the starting position of sMD simulation replicates, in which the peptide was positioned 30 Å away from SAM, right above the peptide binding cleft of SETD2 in an open conformation. b Example of a successful docking of ssK36 into the active site of SETD2 after 50 ns sMD. c Criteria used for definition of a successful docking event derived from the SN2 TS-like conformation. d sMD simulation with an additional, distance-dependent repulsive force of 0.3 kJ/(mol × Å2) between the peptide ends to counteract hairpin formation. e Number of successful docking events in 100 sMD simulations with H3K36 or ssK36 based on the TS-like criteria.

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