Effect of Different Force Fields on B-DNA to A-DNA Conversion†

doi:10.7503/cjcu20180201

Abstract

Abstract:

The aim of the present work is to investigate and compare the effect of the latest CHARMM and AMBER force fields(including bsc1 and OL15) on the B-DNA to A-DNA conversion through exploring the free-energy changes of the conversion process. The extended adaptive biasing force(eABF) method was utilized to perform the free-energy calculations. The results showed that the free-energy profiles characterizing the transition differ significantly for these two force fields. The AMBER force field performs better than the CHARMM force field in aqueous solution. The structure near the global minimum of the free-energy profile by the AMBER force field presents B-form, in agreement with the experimental results, while the most stable structure by the CHARMM force field locates between A- and B-form. Deep analysis of the radial distribution functions of the counterions around DNA reveals that the distribution of counterions in minor groove using the CHARMM force field is lower than that using the AMBER force field. Therefore, for the CHARMM force field, the repulsion of phosphates backbone could not be properly counteracted by counterions, as a result, the minor groove becomes wider, causing a slight conformational change towards A-form.

Key words: B-DNA, A-DNA, Conformational conversion, CHARMM force field, AMBER force field, Free-energy calculation

CLC Number:

O641

TrendMD:

ZHANG Hong, CAI Wensheng, SHAO Xueguang. Effect of Different Force Fields on B-DNA to A-DNA Conversion^†[J]. Chem. J. Chinese Universities, 2018, 39(6): 1205.

Figures/Tables 10

Fig.1 Structures of canonical A-DNA(A) and canonical B-DNA(B)

Fig.2 Free-energy profiles characterizing the B-DNA to A-DNA conversion for the hexamer sequence(AT)6(A) and (GC)6(B)ΔRMSD=-0.3 nm, 0.3 nm denotes an ideal B-DNA, and ideal A-DNA, respectively. a. AMBER-bsc1 force field; b. CHARMM force field; c. AMBER-OL15 force field.

Fig.3 Selected structures near the global minimum of the PMFs for the hexamer sequence (AT)6 (A) AMBER-bsc1 force field; (B) CHARMM force field; (C) AMBER-OL15 force field.

Fig.4 Selected structures near the global minimum of the PMFs for the hexamer sequence (GC)6 (A) AMBER-bsc1 force field; (B) CHARMM force field; (C) AMBER-OL15 force field.

Fig.5 Populations of major-groove widths computed over the 10 ns equilibrium simulation(A) (AT)6; (B) (GC)6. a. bsc1; b. CHARMM; c. X-ray. Properties of crystal structure were computed from the inner six base pairs of PDB code 4J2I and 1QC1.

Fig.6 Populations of minor-groove widths computed over the 10 ns equilibrium simulation(A) (AT)6; (B)(GC)6. a. bsc1; b. CHARMM; c. X-ray. Properties of crystal structure were computed from the inner six base pairs of PDB code 4J2I and 1QC1.

Fig.7 K+/backbone RDF(A), K+/major-groove RDF(B) and K+/minor-groove RDF(C) computed over the 10 ns equilibrium simulation for (GC)6 sequencea. bsc1; b. CHARMM.

Fig.8 K+/backbone RDF(A), K+/major-groove RDF(B) and K+/minor-groove RDF(C) computed over the 10 ns equilibrium simulation for (AT)6 sequence a. bsc1; b. CHARMM.

Fig.9 Water/backbone RDF(A), water/major-groove RDF(B) and water/minor-groove RDF(C) computed over the 10 ns equilibrium simulation for (GC)6 sequence a. bsc1; b. CHARMM.

Fig.10 Water/backbone RDF(A), water/major-groove RDF(B) and water/minor-groove RDF(C) computed over the 10 ns equilibrium simulation for (AT)6 sequence a. bsc1; b. CHARMM.

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