Multistate B- to A- transition in protein-DNA Binding – How well is it described by current AMBER force fields?

Figures & data

Figure 1. Sugar pucker and glycosidic torsion χ in A-DNA, B-DNA and two common intermediate conformers frequently found in protein-DNA complexes, present in dinucleotide conformations AA02 (P/χ = A/B) and BB16 (P/χ = B/A, see ref. Černý et al., 2020).

Table 1. An overview of the DNA force fields used.

Combination	Parent FF	α/γ	β	ε/ζ	χ	Pucker
OL15	parm99^a	bsc0^b	βOL1^c	ε/ζOL1^d	χOL4^e	parm99
OL15χOL3	parm99	bsc0	βOL1	ε/ζOL1	χOL3^f	parm99
bsc1	parm99	bsc0	parm99	bsc1 ε/ζ^g	bsc1 χ^g	bsc1 P^g

^a(Wang et al., 2000), ^b(Perez et al., 2007), ^c(Zgarbová et al., 2015), ^d(Zgarbová et al., 2013), ^e(Krepl et al., 2012), ^f(Zgarbová et al., 2011), ^g(Ivani et al., 2016).

Figure 2. Protein-DNA complexes studied in this work (PDB ID in the parentheses).

Table 2. Selected protein-DNA complexes, resolution of the X-ray structures, groove binding motif (M – major, m – minor) and protein structural element in contact with DNA (h – helix, s – sheet, l – loop). Terminal bases not included in the number of states.

PDB ID	DNA complex with	DNA groove contact	Protein sec. str. contact	Res. [Å]	Number of states with P/χ =
					A/A	A/B	B/A	B/B
1DP7	hRFX1 factor	M/m	h + s + l	1.50	6	0	0	22
1P71	HU architectural factor	m	s + l	1.90	2	2	3	29
1QNE	TATA box binding prot.	m	s + l	1.90	1	9	0	14
2VJV	TnpA transposase	M/m	h + s + l	1.90	19	2	5	30
3AAF	RecQ helicase	M	h + l	1.90	4	1	1	18
3PVI	PvuII endonuclease	M/m	h + s + l	1.59	17	0	0	5
1C8C	Sso7d chromatin prot.	m	m	1.45	0	5	0	7
3KXT	Cren7 chromatin prot.	m	m	1.60	0	3	0	9

Figure 3. Distributions of P and χ in nucleotides representative for B/B (dC106_B, 1C8C), A/B (dC114_C, 1C8C), B/A (dT29_D in 2VJV) and A/A (dC20_C, 2VJV). Dashed vertical lines represent reference values from X-ray (see text).

Figure 4. Sugar pucker and χ in OL15 simulations of selected residues with starting (native) P/χ = A/A state in the 1DP7 complex. Values separating A- and B- type P and χ are shown in pink and cyan, respectively; points on the y-axis indicate X-ray values.

Figure 5. Sugar pucker and χ in OL15 simulations of selected residues with starting (native) P/χ = A/B state in the 3KXT complex. Values separating A- and B- type P and χ are shown in pink and cyan, respectively; points on the y-axis indicate X-ray values.

Figure 6. Sugar pucker and χ in OL15 simulations of selected residues with starting (native) P/χ = B/A state in the 2VJV complex. Values separating A- and B- type P and χ are shown in pink and cyan, respectively; points on the y-axis indicate X-ray values.

Table 3. Percentages of native X-ray P/χ = AA, AB, BA and AB states preserved in MD simulations (time averages over the simulation). Terminal residues were excluded.

PDB ID	% of native X-ray P/χ states preserved in MD simulations
	OL15				bsc1				OL15χOL3
	A/A	A/B	B/A	B/B	A/A	A/B	B/A	B/B	A/A	A/B	B/A	B/B
1DP7	30	–	–	91	61	–	–	90	60	–	–	83
1P71	12	78	46	79	13	64	65	78	16	72	61	70
1QNE	40	95	–	74	63	91	–	70	74	91	–	50
2VJV	37	85	59	84	41	70	66	81	47	75	70	72
3AAF	1	0	14	89	2	0	17	90	4	1	17	80
3PVI	5	–	–	91	3	–	–	87	16	–	–	76
1C8C	–	52	–	97	–	35	–	89	–	47	–	77
3KXT	–	64	–	88	–	54	–	83	–	50	–	72

Table 4. Percentage of P/χ = AA, AB, BA and AB states in MD simulations averaged over all structures, grouped by the native (starting) X-ray state. Populations of native states are highlighted in bold. Terminal residues were excluded.

Native X-ray P/χ state	OL15				bsc1				OL15χOL3
	A/A	A/B	B/A	B/B	A/A	A/B	B/A	B/B	A/A	A/B	B/A	B/B
A/A	21	3	12	64	26	3	17	54	33	3	20	44
A/B	8	74	2	16	15	65	2	18	16	68	2	14
B/A	4	0	50	46	3	0	60	37	7	0	61	32
B/B	5	5	6	84	5	3	10	82	10	5	13	72

Table 5. The propensity for different P/χ states in complexes and in their naked DNA averaged over all OL15 simulations.

Initial state in complex	% P/χ in complex				% P/χ in naked DNA
	A/A	A/B	B/A	B/B	A/A	A/B	B/A	B/B
A/A	21	3	12	64	5	2	7	86
A/B	8	74	2	16	2	2	11	85
B/A	4	0	50	46	2	1	19	78
B/B	5	5	6	84	3	4	7	86

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