DNA and RNA
Best practice guide
HADDOCK supports the docking of nucleic acids, including both DNA and RNA. Currently, only canonical nucleic acid bases are supported. They are listed here.
DNA and RNA nucleotide naming convention
In HADDOCK, DNA and RNA bases must adhere to a strict naming convention to be correctly recognized and interpreted by CNS.
DNA nucleotides:
- Adenosine:
DA - Thymine:
DT - Cytosine:
DC - Guanine:
DG
Note that DNA nucleotides are denoted by two-letter codes, starting at position 18 in the PDB file.
RNA nucleotides:
- Adenosine:
A - Uracil:
U - Cytosine:
C - Guanine:
G
Note that RNA nucleotides are denoted by single-letter codes, starting at position 18 in the PDB file.
Any residue labeled simply as T will be ignored during docking.
If you notice missing thymine residues in your DNA after docking, it is likely that all DNA residues were labeled incorrectly - following the RNA naming convention instead.
This would result in the molecule being treated as RNA rather than DNA.
Publications
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Z. Kurkcuoglu and A.M.J.J. Bonvin. Pre- and post-docking sampling of conformational changes using ClustENM and HADDOCK for protein-protein and protein-DNA systems. Proteins: Struc. Funct. & Bioinformatics, 88, 292-306 (2020).
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R.V. Honorato, J. Roel-Touris and A.M.J.J. Bonvin. MARTINI-based protein-DNA coarse-grained HADDOCKing. Frontiers in Molecular Biosciences, 6, 102 (2019).
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M. van Dijk, K. Visscher, P.L. Kastritis and A.M.J.J. Bonvin. Solvated protein-DNA docking using HADDOCK. J. Biomol. NMR, 56, 51-63 (2013).
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M. van Dijk and A.M.J.J. Bonvin Pushing the limits of what is achievable in protein-DNA docking. Benchmarking HADDOCK's performance.Nucl. Acid Res., 38, 5634-5647 (2010).
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M. van Dijk and A.M.J.J. Bonvin A protein-DNA docking benchmark. Nucl. Acids Res. (2008), 36, e88, doi: 10.1093/nar/gkn386.
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M. van Dijk, A.D.J. van Dijk, V. Hsu, R. Boelens and A.M.J.J. Bonvin Information-driven Protein-DNA Docking using HADDOCK: it is a matter of flexibility. Nucl. Acids Res., 34 3317-3325 (2006).
Tutorials
- Haddock3 basic protein-DNA docking tutorial: This tutorial demonstrates the use of Haddock3 for predicting the structure of a protein-DNA complex in which two protein units bind to the double-stranded DNA in a symmetrical manner (reference structure 3CRO). In addition to provided ambiguous restraints used to drive the docking, symmetry restraints are also defined to enforce symmetrical binding to the protein. This tutorial is using a local version of Haddock3, and therefore requires the use of a terminal and some basic command line expertise.
Optimal settings for docking of nucleic acids
| Module | Parameter | default value | optimal value |
|---|---|---|---|
[rigidbody]: Epsilon constant for the electrostatic energy term | epsilon | 10.0 | 78.0 |
[rigidbody]: Turn off desolvation component term | w_desolv | 1.0 | 0 |
[rigidbody]: Constant dielectric constant | dielec | rdie | cdie |
[flexref]: Epsilon constant for the electrostatic energy term | epsilon | 10.0 | 78.0 |
[flexref]: Turn off desolvation component term | w_desolv | 1.0 | 0 |
[flexref]: Constant dielectric constant | dielec | rdie | cdie |
[flexref]: Turn on automatic DNA base-pair restraints | dnarest_on | false | true |
[flexref]: Reduce TAD factor | tadfactor | 8 | 4 |
[flexref]: Reduce start temperature in 3rd cooling phase | temp_cool3_init | 1000 | 300 |
More about optimal settings for different docking scenarios can be found here.
FAQ
Any more questions about nucleic acids docking with HADDOCK? Have a look at: