Target Prep

Target Prep is LatticeZero's 4-step receptor preparation pipeline. It takes a raw PDB file and produces a compiled scoring grid ready for use with IsoDock and IsoScore — all running in your browser.

Overview

The 4-Step Pipeline

Step 1: Pocket Detection

Define the binding site on your receptor.

Automatic detection: LatticeZero analyzes the protein surface to identify potential binding pockets ranked by volume and druggability score.

Manual definition: Specify the pocket center by:

• Clicking a residue in the 3D viewer
• Entering XYZ coordinates
• Selecting a co-crystallized ligand as the pocket center

Pocket parameters:

• Center — XYZ coordinates of the pocket center
• Radius — distance from center defining the pocket boundary (default: 12 A)
• Padding — additional buffer around the pocket (default: 4 A)

Tip: For best results, use a co-crystallized ligand to define the pocket center. This ensures the grid covers the relevant binding region.

Step 2: Grid Compilation

The scoring grid pre-computes interaction potentials at every grid point within the pocket volume.

What happens:

1. The receptor atoms within the pocket are analyzed
2. For each grid point, all 14 scoring terms are pre-computed
3. The grid is compressed and stored as a .lzgrid file
4. Grid channels: dispersion, repulsion, electrostatics, H-bond donor/acceptor, desolvation, burial, and more

Grid parameters:

• Resolution — grid spacing in Angstroms (default: 0.375 A)
• Channels — which scoring terms to pre-compute (default: all 14)

This step runs on the GPU and typically takes 30-90 seconds.

Step 3: Validation

Automated quality checks on the compiled grid:

• Coverage check — verifies the grid covers the expected pocket volume
• Energy range check — confirms scoring terms are within physical bounds
• Clash detection — identifies grid regions with excessive repulsion
• Channel integrity — verifies all requested channels compiled successfully

If validation passes, you'll see a green checkmark for each test. Warnings (yellow) indicate potential issues but don't prevent usage. Errors (red) require re-running grid compilation with adjusted parameters.

Step 4: Review & Save

Review the prepared target before saving:

• Pocket visualization — see the pocket surface overlaid on the receptor
• Grid statistics — resolution, dimensions, total grid points, file size
• Validation summary — all checks at a glance
• Test score — if a co-crystallized ligand was present, see its predicted score

Click Save to add the prepared target to your project. It's now ready for use with IsoDock and IsoScore.

Working with Prepared Targets

Target Library

Pre-prepared targets from the DEKOIS2 benchmark set are available in the Target Library:

• ACE, EGFR, CDK2, HSP90, MDM2, P38a, and more
• Each includes a compiled grid, validated pocket, and reference actives/decoys
• Ideal for benchmarking and learning the platform

Sharing Targets

Prepared targets are stored within your project. To share:

1. Export the .lzgrid file from the target detail page
2. Share the file with collaborators
3. They import it into their own project

Troubleshooting

Pocket detection finds no pockets

• Ensure your PDB file contains a complete protein structure (not just a fragment)
• Check that water molecules and non-standard residues are present if expected
• Try manual pocket definition with known binding site coordinates

Grid compilation fails or is slow

• Reduce pocket radius if the pocket is very large (>20 A radius)
• Check that WebGPU is active
• Close other GPU-intensive applications

Validation warnings

• "High repulsion in N grid points" — some grid points have very high repulsion, usually near the pocket boundary. This is normal if N is small (<1% of total points).
• "Channel range exceeds threshold" — a scoring term has unusually large values. Check pocket definition and receptor preparation.

Score looks wrong for co-crystallized ligand

• Verify the ligand is correctly positioned within the pocket
• Check that the correct chain and alternate conformations are selected
• Try adjusting the pocket radius to fully encompass the ligand

Best Practices

1. Start with a clean PDB — remove waters, ions, and alternate conformations unless specifically needed
2. Use co-crystallized ligands — they provide the best pocket center definition
3. Check resolution — higher resolution crystal structures generally produce better grids
4. Validate always — never skip Step 3, even for targets that seem straightforward
5. Save intermediate states — you can re-enter Target Prep at any step if you need to adjust parameters