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About DDMut-PPI

DDMut-PPI is a user friendly web server that implements a deep learning approach for predicting effects of missense mutations in protein-protein affinity.


Our method uses an optimised graph-based signature approach to better assess the molecular mechanism of the mutation, by modelling the effects of variations on the inter-residue non-covalent interaction network using graph kernels, evolutionary information, complex network metrics and energetic terms.

Running predictions for single point mutations

User Input Mutations
DDMut-PPI Submission page

The submission page for user input mutations can be accessed via the menu item Run (1) on the top bar menu.

  • The Single Mutation (2) option allows the user to submit one single mutation for prediction.
    • Users are required to provide a wild-type structure (3) by uploading a file in PDB format or providing a PDB accession code.
    • Details on the single mutation are should be provided (4) A mutation code consists of a wild-type code, residue position and mutant code (using the one letter amino acid code). The residue position must be consistent with the PDB file. The chain for the mutation must also be provided.
    • If an email address is provided (5), a link to the results page will be sent to the useras soon as DDMut-PPI finishes processing the submission.
    • An example of the results page is also provided (6).
  • The Mutation List (7) option allows the user to submit a list of single mutations to be analysed by DDMut-PPI in batch.
    • Similarly to the Single Mutation option, a wild-type structure is required (8) and can be input by uploading a file in PDB format or providing a PDB accession code.
    • The list of single-point mutations must be input (9) by uploading a file containing the mutation codes (chain identifier, wild-type residue code, position and mutant residue code). The file format requires one mutation mutation per line. A sample file is also provided.
    • If an email address is provided (10), a link to the results page will be sent to the useras soon as DDMut-PPI finishes processing the submission.
    • An example of the results page is also provided (11).
Interface Analysis
DDMut-PPI Interface Submission page

The submission page for automated interface analysis can be accessed via the menu item Run (1) on the top bar menu.

  • Users are required to provide a wild-type structure (2) by uploading a file in PDB format or providing a PDB accession code.
  • On Mutation Details section (3), one is required to provided which type of analysis to run. Here two options are available: Alanine Scanning (mutate all residues at the interface to Alanine) or Saturation Mutagenesis (mutate all residues at the interface to all 19 standard amino acids).
  • If an email address is provided (4), a link to the results page will be sent to the useras soon as DDMut-PPI finishes processing the submission.
  • An example of the results page is also provided (5).

Results for single point mutations

Single Mutation
DDMut-PPI Single Mutation Prediction page 1 DDMut-PPI Single Mutation Prediction page 2 DDMut-PPI Single Mutation Prediction page 3

The results page for a single mutation will be shown once computations are completed in 3 different panels.

  • On the first panel, the ΔΔG is displayed (1) alongside with the details on the mutation being analysed (2).
  • The second panel will show and interactive 3D viewer (3), which allows user to analyse the interatomic interactions between the wild-type residue and nearby residues. Interactions can be hidden or displayed using the controles provided (4). The viewer can also be manipulated using buttons at the bottom of the panel (5).
  • Lastly, on the third panel, DDMut-PPI allows users to analyse the inter-residue interactions of wild-type and mutant(6). Here, a set of switches are also provided (7) to allow customisation of the interactions being displayed on the side box(8).
Mutation List
DDMut-PPI Mutation List Prediction page

The results page for a list of single mutations will be shown once computations are completed in a single table.

  • The predicted ΔΔG for every single-point mutation will be displayed on a table (1). A set of controls for sorting based on columns and an input for text search are also provided.
  • All the analysis discussed for the Single Mutation option can be analysed for each single mutation on the table through the Details button (2) of each row.
  • Results can be downloaded as a .csv file by clicking on the Download button on the top right corner (3).
Interface Analysis
DDMut-PPI Interface Submission page
Alanine Scanning
DDMut-PPI Alanine Scanning Results page 1 DDMut-PPI Alanine Scanning Results page 2 DDMut-PPI Alanine Scanning Results page 3

The results page for Alanine Scanning will be displayed in three different panels.

  • The predicted ΔΔG for every single-point mutation to Alanine will be displayed on a table (1) on the first panel. A set of controls for sorting based on columns and an input for text search are also provided.
  • Results can be downloaded as a .csv file by clicking on the Download button on the top right corner (2).
  • All results are also summarised on a bar plot on the second panel (3). Positive and negative ΔΔG predictions are shown in in blue and red, respectively.
  • The third panel will show and interactive 3D viewer (4) in which the interface residues are colored according to the ΔΔG predictions. The viewer can be customised using the controls on the top of the panel (5). A set of buttons are displayed at the bottom of the panel (6) to adjust visualisation.
Saturation Mutagenesis
DDMut-PPI Saturation Mutagenesis Results page 1 DDMut-PPI Saturation Mutagenesis Results page 2 DDMut-PPI Saturation Mutagenesis Results page 3

The results page for Saturation Mutagenesis will also be displayed in three different panels.

  • The predicted ΔΔG for every single-point mutation to Alanine will be displayed on a table (1) on the first panel. A set of controls for sorting based on columns and an input for text search are also provided.
  • Results can be downloaded as a .csv file by clicking on the Download button on the top right corner (2)
  • All results are also summarised on a heatmap plot on the second panel (3) which can be downloaded as an image file (4).
  • The third panel will show and interactive 3D viewer (5) in which the interface residues are colored according to the average ΔΔG predictions values. The viewer can be customised using the controls on the top of the panel (6). A set of buttons are displayed at the bottom of the panel (7) to adjust visualisation.

Running predictions for multiple point mutations

Home page DDMut-PPI

The input page can be accessed from the top menu Run (1).

Users are required to provide a protein structure by uploading a file in PDB format or typing a PDB four letter accession code (2).

Two prediction types are available (3):

  • Manual: This option allows for the input of specific multiple mutations which can be provided via the text field or by uploading a plain text file with a list of entries. In both cases, multiple mutations are must be separated by a semi-colon (;) and one entry per line. Input examples and a sample file are available.
  • Systematic: If this option is selected, users are required to provide a chain identifier from which interfaces residues will be identified and all permutations of double and triple mutants generated for evaluation. The results page will show top 100 entries increasing affinity and top 100 decreasing affinity.

If provided (4), an email will be sent to the user after the submission is processed.

A button for an example results page is available at the bottom of the form (5)

Results for multiple point mutations

Table in results page DDMut-PPI
  • For both types of prediction (manual and systematic), results are shown in table format (6) where entries predicted as increasing affinity are shown in blue and decreasing affinity in red. Individual ΔΔGBinding for each point mutation can also be viewed by clicking the button visibility. These are calculated using DDMut-PPI single mutation model.
  • A button for downloading (7) all the results as a comma separated file (csv) is available
  • Systematic evaluations of PPI interface shows the top 100 increasing/decreasing affinity entries based on all permutations of double and triple mutants at one side of a protein-protein interface.
Interactive viewer in results page DDMut-PPI
  • An interactive 3D viewer is available (8) allowing for the analysis of interatomic interactions for the wild-type residues. A set of controls are also available for customising the viewer (9)
  • Action buttons at the bottom of the viewer (10)

Contact us

In case you experience any trouble using DDMut-PPI or if you have any suggestions or comments, please do not hesitate in contacting us via our Group website.

If your are contacting regarding a job submission, please include details such as input information and the job identifier