Glossary

Key terms, metrics, and definitions used throughout LatticeZero.

Active (compound)

A molecule experimentally confirmed to bind to the target protein. In benchmarking, actives are the "positives" that a scoring function should rank highly.

AUC (Area Under the ROC Curve)

A metric ranging from 0 to 1 that measures how well a scoring function separates actives from decoys. AUC = 1.0 means perfect separation; AUC = 0.5 means random (no better than chance). LatticeZero uses tie-corrected Mann-Whitney U AUC.

BEDROC (Boltzmann-Enhanced Discrimination of ROC)

An enrichment metric that weights early recognition more heavily than AUC. Useful when you care most about finding actives in the top 1-5% of a ranked list. Uses an exponential decay parameter alpha (default: 20).

Binding Pocket

The 3D cavity on a protein surface where ligands bind. In LatticeZero, the pocket is defined by a center point and radius during Target Prep. The scoring grid covers this region.

Bootstrap Confidence Interval

A statistical method for estimating uncertainty. LatticeZero resamples actives and decoys with replacement (typically 1,000 iterations) to compute a 95% confidence interval around AUC and other metrics.

Clash

A steric overlap between atoms. The E_clash scoring term penalizes ligand atoms that are too close to protein atoms. Moderate clashes may indicate pose prediction issues; severe clashes suggest the pose is physically unrealistic.

Cross-Validation (Holdout)

A validation technique where data is split into training and test sets. The Optimizer uses multi-seed 5-fold holdout: it trains on 80% of ligands and evaluates AUC on the held-out 20%, repeating 5 times. The mean holdout AUC is the primary quality metric.

Decoy

A molecule designed to resemble actives in physicochemical properties (molecular weight, logP, hydrogen bond count) but not bind to the target. Decoys are the "negatives" in benchmarking. DEKOIS2 provides carefully matched decoy sets.

DEKOIS2

Demanding Evaluation Kits for Objective In Silico Screening, version 2. A widely-used benchmark suite providing curated active/decoy sets for dozens of pharmaceutical targets. LatticeZero validates scoring profiles against DEKOIS2 targets.

Desolvation

The energetic cost of removing water molecules from both the ligand and the protein surface upon binding. Represented by the E_desolv scoring term.

Differential Evolution (DE)

The global optimization algorithm used by the LatticeZero Optimizer. DE maintains a population of candidate solutions and evolves them through mutation, crossover, and selection. It's robust against local minima and doesn't require gradient information.

Dispersion

Attractive van der Waals interactions between atoms. The E_disp term captures London dispersion forces, which are distance-dependent and contribute favorably to binding. Dominant for hydrophobic contacts.

Docking

The computational process of predicting how a small molecule (ligand) binds to a protein target. IsoDock performs docking using a genetic algorithm to search for optimal poses.

Enrichment Factor (EF)

A metric measuring how many more actives are found in the top X% of a ranked list compared to random selection. EF1% = 20 means the top 1% contains 20x more actives than expected by chance.

Feature Matrix

In the Optimizer, a pre-computed N x F matrix where N = number of ligands and F = number of scoring features. Used for fast vectorized scoring: scores = feature_matrix @ weight_vector.

Genetic Algorithm (GA)

The pose search method used by IsoDock. A population of candidate poses evolves through selection, crossover, and mutation until convergence. Parameters include population size, mutation rate, and maximum generations.

Golden Pack

A pre-validated target bundle containing a compiled scoring grid, optimized profile, reference compounds, and benchmark results. Golden Packs provide production-ready scoring for well-studied targets.

Grid (Scoring Grid)

A 3D lattice of pre-computed interaction energies covering the binding pocket. During scoring, each ligand atom's contribution is looked up from the grid, enabling ultra-fast evaluation. Compiled during Target Prep.

Hydrogen Bond

A directional electrostatic interaction between a hydrogen donor (N-H, O-H) and an acceptor (lone pair on N, O, S). The E_hbond term scores these interactions. The hbondGeo term evaluates the geometric quality (angle and distance) of hydrogen bonds.

L2 Regularization

A penalty added to the Optimizer's objective function that discourages extreme weights: lambda * ||w||^2. Prevents overfitting and keeps profiles physically interpretable.

Ligand

A small molecule that binds to a protein target. In molecular docking, ligands are the molecules being scored against the receptor.

Metalloprotease

A protease that uses a metal ion (typically zinc) in its catalytic mechanism. ACE is the canonical example in LatticeZero. Metal coordination scoring is important for these targets.

Pose

A specific 3D orientation and conformation of a ligand within the binding pocket. Docking generates poses; scoring evaluates them.

Profile (Scoring Profile)

A set of 14 weights that control how each physics term contributes to the total score. Different profiles are optimized for different target classes. See Scoring Profiles.

Receptor

The protein target that ligands bind to. Used interchangeably with "target" in the context of molecular docking.

Repulsion

Short-range steric clash energy. The E_rep term penalizes atoms that are closer than the sum of their van der Waals radii. High repulsion indicates steric clashes in the pose.

Rescoring

Evaluating pre-existing ligand poses against a scoring function without performing new pose search. IsoScore is a rescoring engine — it takes 3D poses as input and returns scores.

ROC Curve (Receiver Operating Characteristic)

A plot of true positive rate (sensitivity) vs. false positive rate (1 - specificity) at varying score thresholds. The area under this curve (AUC) quantifies overall discrimination ability.

Scoring Function

The mathematical function that evaluates how well a ligand pose fits the target binding site. LatticeZero's scoring function has 14 physics-based terms. The total score is a weighted sum of these terms.

SDF (Structure-Data File)

A file format for storing molecular structures with optional data fields. LatticeZero accepts SDF files as input for scoring and can export results in SDF format.

Strain

Internal ligand strain energy — the energetic cost of the ligand adopting its bound conformation relative to a relaxed state. High strain suggests the ligand must distort to fit the pocket, which is thermodynamically unfavorable.

Target Class

A classification of protein targets by structural and functional similarity (e.g., kinase, protease, nuclear receptor). Target class guides the selection of scoring profiles and Optimizer priors.

Tier

A quality classification for scoring profiles based on AUC: Platinum (>= 0.90), Gold (>= 0.80), Silver (>= 0.60), Bronze (< 0.60).

WebGPU

A modern web standard (W3C) for GPU computation in browsers. WebGPU provides low-level access to the GPU for both graphics and compute workloads. LatticeZero uses WebGPU compute shaders for scoring function evaluation.

Weight (Profile Weight)

A numeric multiplier applied to a scoring term within a profile. Higher weight = greater influence on the total score. Weights are optimized by the Optimizer to maximize active/decoy discrimination.