Amino Acid–Nucleotide Interactions Web Server

This web server allows the user to view the interaction energies of amino acid–DNA residue pairs extracted from the structures of protein–DNA complexes in the RCSB PDB [1]. When one transforms all amino acid–DNA residue pairs of a certain type (for example, all contacts of asparagine with adenine) so that the RMSD of atomic positions of the DNA base atoms is minimised, one obtains a three-dimensional distribution of that amino acid around that DNA base. Due to geometrical and energetical constraints, some amino acid side chains in these distributions will be found in spatially defined clusters. In each side chain cluster within each distribution, a single amino acid–DNA residue pair, called the cluster representative, can be defined as the pair containing the amino acid side chain which has to lowest RMSD of atomic positions from all the other members of that cluster. The detailed description of the data set and the process of cluster definition are both described in refs. [2] and [3].

The purpose of this web server is to provide the user with the knowledge of how a specific geometrical configuration of some amino acid–DNA residue contact relates to the background of all contacts of that type. Specifically, the user can view how abundant the configuration is in the set of protein–DNA complexes, what its interaction energy is, and how large that interaction energy is when compared to the other interaction energies in that particular distribution. The interaction energy calculations were performed using a molecular mechanical force field and, where applicable, an implicit solvent, and are described in detail in ref. [3].

In the menu on the right, one can choose the parameters of the amino acid–DNA residue distribution one is interested in. Starting from the top, the [option]s enable the user to select:

  1. [DNA residue moieties:] base / base + sugar-phosphate — specifies whether one is interested in the interaction energy of the amino acid side chain with the specified DNA base, or with the whole nucleoside monophosphate (that is, specifies whether the sugar-phosphate moiety is ignored in the interaction energy calculation or not)
  2. [Relative permittivity:] 1 / 4 / 16 / 80 — specifies the dielectric constant of the implicit solvent used in the interaction energy calculation (for details of the implementation, see ref. [3])
  3. [Interaction directionality restrictions:] base-directed contacts/none (all contacts) — specifies whether the background distribution should involve only the amino acid–DNA residue pairs in which the amino acid side chain contacts the DNA base moiety, or whether the pairs featuring contacts with the DNA sugar-phosphate should be included as well
  4. [Amino acid:] (amino acid name) — specifies the amino acid side chain for which the interaction energy profile and visualisation should be retrieved
  5. [DNA base type:] adenine / guanine / cytosine / thymine — specifies the type of DNA base for which the interaction energy profile and visualisation should be retrieved
  6. [Redundancy level:] 100% / 95% / 90% / 30% — specifies the maximum sequence identity of any pair of protein sequences from which the amino acids in the distribution are drawn

After clicking "Submit", a histogram of interaction energies of the amino acid–DNA residue pairs from the selected distribution (the interaction energy profile) is drawn on the left side of the screen. The numbers along the x-axis show the middle interaction energy of the contacts represented by that column. The height of each column represents the number of contacts falling into the interaction energy range of that column. These numbers can also be retrieved when mousing over each column. If at least one amino acid side chain cluster exists in the distribution with chosen parameters, part of one or more columns will be coloured blue. This corresponds to the contacts from that cluster having the interaction energy within the range represented by that column. If more than one cluster exists given the selected set of parameters, the cluster of interest can be chosen using the [Cluster:] option in the top left corner. Up to six clusters can be selected for each distribution.

If some cluster is available and selected from the selection menu at the top left of the screen, the middle part of the screen will display the three-dimensional representation the set of amino acid–DNA residue pairs from that cluster and with the parameters chosen in the right part of the screen. The pair containing the cluster representative will be drawn using thick sticks and its three-dimensional coordinates can be downloaded in the ".pdb" format after clicking the "Download representative" button. Clicking the "Download cluster" lets one download the 3-D coordinates of all members of that cluster, with the properties of the DNA residue selected using the "[DNA residue moieties:]" button in the right menu. Clicking the "Download all" button (available even when no cluster is selected) lets one obtain the 3-D coordinates of all amino acid–DNA residue pairs in the distribution, with the parameters of the DNA residue chosen using the "[DNA residue moieties:]" button, and the set of amino acid side chains chosen using the "[Interaction directionality restrictions:]" button on the right.

References:

  1. Bernstein,F.C., Koetzle,T.F., Williams,G.J., Meyer,E.F., Brice,M.D., Rodgers,J.R., Kennard,O., Shimanouchi,T. and Tasumi,M. (1977) The Protein Data Bank. Eur. J. Biochem., 80, 319–324.
  2. Jakubec,D., Hostaš,J., Laskowski,R.A., Hobza,P. and Vondrášek,J. (2015) Large-Scale Quantitative Assessment of Binding Preferences in Protein–Nucleic Acid Complexes. J. Chem. Theory Comput., 11, 1939–1948.
  3. Jakubec,D., Laskowski,R.A. and Vondrášek,J. (2016) Sequence-Specific Recognition of DNA by Proteins: Binding Motifs Discovered Using a Novel Statistical/Computational Analysis. PLoS One, 11, e0158704.