DOCK Denovo Run

Dock Denovo Run

The Denovo module of DOCK is a relatively new feature (as of Fall 2016) that constructs new ligand molecules inside a protein active site from a library of user-specified "fragments". These fragments are common chemical functional groups, or building blocks, that are typically selected from a ZINC library of millions of compounds based off of their frequency of appearance. These fragments are classified as scaffolds, linkers, or side chains, according to the number of atomic positions that are permitted to seed growth: 3, 2, and 1 atoms, respectively. Thus, a scaffold could seed growth on three different atoms, having three linkers bonded to each position, and a linker could seed growth on two positions, and a side-chain on one position.

Once the molecules are built within the active site, their interactions with the protein are scored using the user-specified method of scoring. This tutorial will walk through the steps needed to run a Denovo calculation on the Beta Trypsin system from the 2016 DOCK tutorial. This method will utilize the multi-grid scoring function, called through the descriptor score.

Preparing The Files

Before the Denovo module can be run, please ensure you have ran the DOCK 2016 tutorial and have all the resulting files. The tutorial can be accessed through here.

You should have these files in your directory:

001.files:

    1BJU.pdb
    1BJU.lig.mol2
    1BJU.rec.clean.mol2
    1BJU.rec.noH.mol2
    selected_spheres.sph

In order to run Denovo with multigrid scoring, we must first go through several steps:

1). Create a primary residue text file and a reference text file -- selects the primary residues of interest

2). Make a multigrid file for each specified residue -- forms a grid for each residue specified in previous step

3). Minimizes ligand mol2 file using multigrids from previous step

4). Rescores ligand on multigrid to yield a minimized ligand .mol2 file. This serves as the reference ligand for Denovo calculations.

Luckily, our good friend Brian generated some extremely robust scripts to make this process easier. There is one script for each step.