Molecular Dynamic of Various DNA Sequences Binding of Dithienylethenes†

doi:10.7503/cjcu20180837

Abstract

Abstract:

Binding modes between various DNA sequences and stereoisomeric rotamers of two dithienylethene derivatives(DTE1 and DTE2) representing photochromic switches were investigated in terms of molecular dynamics simulations and characterized by their binding energies. The result shows that minor groove binding(MiGB) is found to be the most robust binding mode between DNA and DTE(either DTE1 or DTE2). Due to steric hindrance, two DTE derivatives that are rotatable isomers exhibit distinct binding behaviors to DNA, and thus DNA has significant enantioselectivity for DTE derivatives. Moreover, the selectivity of the DTE derivative to the binding site of the DNA molecule is directly related to the base pair constitution, providing accurate theoretical guidance for precision medicine by chiral drugs based on this molecule.

Key words: Molecular dynamics, Chiral drug, Dithienylethene, DNA, Rotamer, Binding mode

CLC Number:

O641.3

TrendMD:

SUN Haofan,ZHANG Lingyi,PATRICK Norman,ZHANG Weibing. Molecular Dynamic of Various DNA Sequences Binding of Dithienylethenes^†[J]. Chem. J. Chinese Universities, 2019, 40(6): 1229.

Figures/Tables 9

References 27

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Conformation	Binding position
Conformation	MaGB	MaGI	MiGB	MiGI
P-DTE1	MaGB	MaGI	MiGB	MiGI
M-DTE1	MiGB	MaGI	MiGB	MiGI
P-DTE2	Bottom binding	MaGI	MiGB	MiGB
M-DTE2	MiGB	MaGI	MiGB	MiGB

Conformation	Binding position
Conformation	MaGB	MaGI	MiGB	MiGI
P-DTE1	MaGB	MaGI	MiGB	MiGI
M-DTE1	MiGB	MaGI	MiGB	MiGI
P-DTE2	Bottom binding	MaGI	MiGB	MiGB
M-DTE2	MiGB	MaGI	MiGB	MiGB

Conformation	Binding position
Conformation	MaGB	MaGI	MiGB	MiGI
P-DTE1	MiGB	MaGI	MiGB	MiGI
M-DTE1	MiGB	MaGI	MiGB	MiGI
P-DTE2	Bottom binding	MaGI	MiGB	MiGI
M-DTE2	Bottom binding	MaGI	MiGB	Bottom binding

Conformation	Binding position
Conformation	MaGB	MaGI	MiGB	MiGI
P-DTE1	MiGB	MaGI	MiGB	MiGI
M-DTE1	MiGB	MaGI	MiGB	MiGI
P-DTE2	Bottom binding	MaGI	MiGB	MiGI
M-DTE2	Bottom binding	MaGI	MiGB	Bottom binding

DNA	Conformation	Final position	E_coul/(kJ·mol^-1)	E_vdW/(kJ·mol^-1)
(6A-T +6C-G)×2	P-DTE1	No favorable binding	-259±75	-84±21
	M-DTE1	MiGB(A-T)	-828±71	-217±17
	P-DTE2	MiGB(between A-T and C-G)	-660±100	-113±21
	M-DTE2	MiGB(between A-T and C-G)	-598±88	-121±25