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PinaColada: Peptide-Inhibitor Ant Colony Ad-hoc Design Algorithm.

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Overview

PinaColada is a peptide design algorithm used for:
    (i) Design better binding peptides given a protein-peptide complex.
    (ii) Design good binding peptides, with an initial template being extracted from the protein biding site.
    (iii) Design good binding peptides to fit the given binding site on the protein.
The algorithm requires as input a 3D complex structure (protein-protein OR protein-peptide OR protein + binding site) given as a pdb file.
For option (iii) the binding site is given in the format of a text file, with the appropriate number of residues. Example could be downloaded here:

Input Fields

  • Input file content:
    Protein-protein complex OR protein-peptide complex OR protein + binding site.
    In the protein-protein option, PinaColada will derive a suitable peptide from the ligand chain, and will use this peptide as an initial template.
    In the protein+binding site option, PinaColada will use PatchDock to dock a poly-alanine peptide into the given binding site, and will use this peptide as an initial template.

  • Complex PDB file:
    A file containing the complex in .pdb format.
    The file should contain a single pdb model of the complex. The algorithm adds hydrogen atoms to the complex so there is no need to add them manualy.

  • Options level:
    The extended option should be used in the following cases:
    i) If you want to change the ant colony parameters, in order to speed up the algorithm by reducing the number of ants/rounds. ii) If you want to get more than 50 peptide suggesions. iii) If you want to upload biological constraints (explanation followed).
  • Receptor chain(s):
    One chain or more of the receptor protein.
    One letter for each chain.

  • Ligand chain:
    The chain of the ligand (peptide or protein).
    A single letter chain.

  • Binding site constraints:
    This is allowed only in protein+binding site mode.
    The file should be in the following format:
    363 B
    364 B
    365 B
    366 B
    386 B
    388 B
    410 B
    411 B
    433 B
    458 B
    507 B
    533 B
    where the numbers are the residue numbers, and the letter is the appropriate chain.
    An example file could be downlaoded here:

  • Peptide length:
    You should specify the length of the peptide you want to receive. (5 - 15).
    In protein-peptide mode, just write the length of the peptide in the complex.

  • Number of rounds:(extended options)
    The number of rounds of the ant colony optimization.
    The lower it is set, the faster it will run, but the output will be less converged.

  • Number of ants per round:(extended options)
    The number of rounds of the ant colony optimization.
    The lower it is set, the faster it will run, but the output will be less converged.

  • Number of output peptides:(extended options)
    The number of best overall ants PinaColada will output.

  • Biological constraints:(extended options)
    The file should be in the following format:

    Fixed acids [-1,-2,-2,-1,-1,-2,-1,[0,1,4],-1,-1]
    Maximal num [[[14], 0], [[0,9,10,12,13,17,19], 3], [[1,2,3,5,6,8,11,15,16,18], 7]]
    Minimal num [[[1,3,5,8,11], 2]]
    Groups ratio [[[2,3,4,7,16],[0,1,10,11,12],1]]

    Notes:
    In each line, Between each title and list should be a tab. Space will not work.
    Fixed acids: -1 stands for all residues. -2 stands for do NOT change current residue, and [x,y,z,...] stands for allowing only those residues in that position.
    Use fixed acids contraints only for specific positions and not for the whole peptide. The algorithm is meant to choose the best amino acids in each position and is not adopted to design out of harsh constraints.
    Maximal num: for limiting the number of a group of amino acids, add [[x,y,z,...],w] to limit the number of {x,y,z,...} to w.
    Minimal num: for forcing a group of amino acids, add [[x,y,z,...],w] to force at least w residues out of {x,y,z,...}.
    Groups ratio: add [[x1,y1,z1,...],[x2,y2,z2,...],w] if you want that for each residue out of {x1,y1,z1,...} there will be at least w residues out of {x2,y2,z2,...}.
    For recommended constraints for solubility, hydrophobicity and hilicality, use the example above, and change only the Fixed acids, to fit the peptide's length.
    For residue to number translation, please see the following table:
    Please check if your PDB files are in the right PDB format. See PDB website for format description.
    The program will not work with PDB file that is not in the right format.

  • Email address:
    PinaColada results will be sent to you via Email. Please verify that you type in the correct email address.


    Output

    Once PinaColada is done, an email will be sent to you containing a .zip file with all the result files.
    If you get an empty Best.log file, it could mean that all the mutations got a positive binding energy (which means non binding).
    Also, if you did not get any results while trying a very long peptide (10 or more amino acids), you are recommended to try shorter peptides.


    Run time

    PinaColada run time depends on two main factors - peptide size and server workload.
    A single run should take not more than 24 hours.
    If you would like your results faster, you could reduce the number of rounds, and ants per round, on Advanced Options.