Problem of finding all base pairs in distorted DNA structure using 3DNA

[wang2012]

Hello Xiang-Jun,

In order to find all base pairs, I have changed the values in misc_3dna.par  to calculate the non-WC b.p in much distorted structure. I artificially increased all the values based on my understanding of these parameters.
Still, sometimes, find_pair program in 3DNA can not find all the pairs even through they are structurally very similar. An example is shown below to demonstrate the problem. The two 12-mer structures (md5.1004.mod.pdb and md5.1016.mod.pdb) are obtained from a molecular dynamics simulation at 1004 and 1016 ps.

So the question is how to change the parameter file to analyze all base pairs in these structures?

Difei

================
Changes in Misc_3dna.par
100.0 0.0 ON A1 # upper H-bond length limits/atoms, alternative location
100.0          # max. distance between paired base origins (FIND_PAIR)
100.0           # max. vertical distance between paired base origins (FIND_PAIR)
90.0          # max. angle between paired bases [0-90] (FIND_PAIR)
2.5           # MIN. distance between RN9/YN1 atoms (FIND_PAIR)
100.0          # max. distance criterion for helix break (FIND_PAIR)
0.6           # r7 criterion to decide if a helix is curved
3.2           # r8 H-bond distance for water molecules with base N/O atoms
10.50           # r9 maximum O3'--P distance for linkage (REBUILD)

Output files from find_pair in 3DNA

md5.1004.mod.pdb
md5.1004.mod.out
    2         # duplex
   11         # number of base-pairs
    1    1    # explicit bp numbering/hetero atoms
    1   24  0 #    1 | A:...1_:[..C]C-----G[..G]:..24_:B  0.99  0.99 20.12  9.24  1.47
    2   23  0 #    2 | A:...2_:[..G]G-----C[..C]:..23_:B  0.79  0.72 12.67  8.99  0.73
    3   22  0 #    3 | A:...3_:[..C]C-----G[..G]:..22_:B  0.21  0.16  4.17  9.00 -0.97
    4   21  0 #    4 | A:...4_:[..G]G-----C[..C]:..21_:B  0.36  0.09 16.09  9.09 -0.97
    5   20  0 #    5 | A:...5_:[..C]C-----G[..G]:..20_:B  0.61  0.33  6.50  9.12 -0.22
    6   19  0 #    6 | A:...6_:[..C]C-----G[..G]:..19_:B  0.25  0.05 14.46  9.00 -1.15
    7   18  0 #    7 | A:...7_:[..A]A-----T[..T]:..18_:B  1.00  0.96 38.08  8.78  1.41
    8   17  0 #    8 | A:...8_:[..A]A-----T[..T]:..17_:B  0.43  0.24 17.20  8.74 -0.58
    9   16  0 #    9 | A:...9_:[..C]C-----G[..G]:..16_:B  0.26  0.25 14.19  9.27 -0.73
   10   15  0 #   10 | A:..10_:[..G]G-----C[..C]:..15_:B  0.63  0.28 21.27  9.16 -0.31
   11   14  0 #   11 | A:..11_:[..C]C-----G[..G]:..14_:B  0.41  0.01 23.73  8.95 -1.07
##### Base-pair criteria used: 100.00100.00100.00 90.00  2.50100.00
##### 0 non-Watson-Crick base-pairs, and 1 helix (0 isolated bps)
##### Helix #1 (11): 1 - 11

md5.1016.mod.pdb
md5.1016.mod.out
    2         # duplex
   12         # number of base-pairs
    1    1    # explicit bp numbering/hetero atoms
    1   24  0 #    1 | A:...1_:[..C]C-----G[..G]:..24_:B  0.36  0.06 20.92  9.18 -1.01
    2   23  0 #    2 | A:...2_:[..G]G-----C[..C]:..23_:B  0.44  0.42 18.28  9.14 -0.22
    3   22  0 #    3 | A:...3_:[..C]C-----G[..G]:..22_:B  0.77  0.31 20.29  9.10 -0.11
    4   21  0 #    4 | A:...4_:[..G]G-----C[..C]:..21_:B  0.34  0.01  2.58  8.97 -1.15
    5   20  0 #    5 | A:...5_:[..C]C-----G[..G]:..20_:B  0.58  0.58 12.03  9.19  0.23
    6   19  0 #    6 | A:...6_:[..C]C-----G[..G]:..19_:B  0.26  0.20  6.49  9.04 -0.85
    7   18  0 #    7 | A:...7_:[..A]A-----T[..T]:..18_:B  0.94  0.91 22.58  8.69  1.26
    8   17  0 #    8 | A:...8_:[..A]A-----T[..T]:..17_:B  0.71  0.70 22.61  8.72  0.61
    9   16  0 #    9 | A:...9_:[..C]C-----G[..G]:..16_:B  0.59  0.54  3.06  9.03  0.17
   10   15  0 #   10 | A:..10_:[..G]G-----C[..C]:..15_:B  0.56  0.42  7.20  9.02 -0.11
   11   14  0 #   11 | A:..11_:[..C]C-----G[..G]:..14_:B  0.62  0.05 15.44  8.93 -0.79
   12   13  0 #   12 | A:..12_:[..G]G-*---C[..C]:..13_:B  5.49  4.72 76.16  7.78 14.93
##### Base-pair criteria used: 100.00100.00100.00 90.00  2.50100.00
##### 1 non-Watson-Crick base-pair, and 1 helix (0 isolated bps)
##### Helix #1 (12): 1 - 12

[xiangjun]

Hi Difei,

Thanks for posting your question in the new 3DNA forum!

You've raised a very subtle, yet interesting and significant point w.r.t. to find_pair. There are several aspects to address the issue you experienced, as follows:

• There is actually one more (undocumented) 'sanity' check for base pair than those specified in the file 'misc_3dna.par': the overlap area between the two bases. The current fixed setting is 0.01 Ų, i.e., virtually allowing for no overlap. The 'missing pairs' in the two sample structures all have overlap areas over the criterion, which explains why you cannot find it by manipulating the various parameters in 'misc_3dna.par'. See attached figure for the pair A12_G with B13_C in 'md5.1004.mod.pdb' you emailed me.
• From my understanding of the term, I certainly won't classify such extreme cases as base pairs: base-overlapping is associated with stacking (vertical) instead of pairing (plannar). That's why I've not documented this criterion, but internally checked for it.
• To 'force' such pairs, it is best to first run find_pair on the structure (or a representative from an ensemble) and then make manual changes as necessary. The analysis routines in 3DNA, analyze/cehs, will calculate relevant parameters accordingly (indeed, of any arbitrary pair). The topic has shown up repeatedly in the forum, especially with regard to the analysis of NMR ensemble or MD trajectories. See the section "Molecular dynamics simulations".
• To allow for more flexibility,  it may be desirable (at least won't hurt) to have the overlap criterion also available in 'misc_3dna.par'. Do you want to try this? If so, please let me know your OS so I can provide you a test version.

HTH,

Xiang-Jun

[wang2012]

Hello Xiang-Jun,

I think there is no need to change more in misc_3dna.pair since manually changing the output of find_pairs does the trick.
Thanks!

Difei

[guchan]

Hello Xiang-Jun and Difei,
    I have the same problem with Difei and I tried to look for solutions in Simulation part of 3DNA Forum according to Xiang-Jun's suggestion, but I didn't find the exact steps to solve the problem.
    Could you please give me a hyperlink? Many thanks!

Chan Gu

[xiangjun]

What 'same problem' do you have? As shown in Difei's last post on this thread, his problem has been solved.

Please start a new topic, and be specific with your problem by providing a reproducible example.

Xiang-Jun