amina-cli 0.4.3__tar.gz → 0.5.1__tar.gz

{amina_cli-0.4.3 → amina_cli-0.5.1}/PKG-INFO

@@ -1,6 +1,6 @@
 Metadata-Version: 2.4
 Name: amina-cli
-Version: 0.4.3
+Version: 0.5.1
 Summary: CLI for AminoAnalytica protein engineering platform
 Project-URL: Homepage, https://aminoanalytica.com
 Project-URL: Documentation, https://docs.aminoanalytica.com

{amina_cli-0.4.3 → amina_cli-0.5.1}/pyproject.toml

@@ -1,6 +1,6 @@
 [project]
 name = "amina-cli"
-version = "0.4.3"
+version = "0.5.1"
 description = "CLI for AminoAnalytica protein engineering platform"
 readme = "README.md"
 license = {text = "Apache-2.0"}

{amina_cli-0.4.3 → amina_cli-0.5.1}/src/amina_cli/__init__.py

@@ -9,4 +9,4 @@ Quick start:
     amina run esmfold --sequence "MKFLILLFNILCLFPVLAADNH"
 """
 
-__version__ = "0.4.3"
+__version__ = "0.5.1"

{amina_cli-0.4.3 → amina_cli-0.5.1}/src/amina_cli/commands/tools/design/docs/proteinmpnn.yaml

@@ -28,41 +28,43 @@ when_not_to_use: |
 tool_algorithm: |
   ProteinMPNN is an autoregressive message-passing neural network that designs
   amino acid sequences conditioned on a protein backbone structure. The model
-  operates on a k-nearest-neighbor graph constructed from C-alpha coordinates
-  and iteratively passes messages between nodes (residues) and edges (spatial
-  neighbors).
+  is backbone-only (it never sees side-chains) and operates on a
+  k-nearest-neighbor graph over Cα atoms.
 
   Key stages:
   1. **Graph construction**: The input PDB backbone is converted to a
-     k-nearest-neighbor graph based on C-alpha distances.
-  2. **Encoder**: A series of message-passing layers encode structural features
-     (backbone dihedrals, inter-residue distances, orientations) into node and
-     edge embeddings.
-  3. **Decoder**: An autoregressive decoder samples amino acid identities one
-     residue at a time, conditioned on the structural encoding and previously
-     sampled residues.
+     k-nearest-neighbor graph (k=48) over Cα atoms; edge features encode
+     distances between N, Cα, C, O, and a virtual Cβ.
+  2. **Encoder**: 3 message-passing layers with hidden dim 128 encode
+     backbone geometry into node and edge embeddings.
+  3. **Decoder**: 3 message-passing layers autoregressively sample amino-acid
+     identities one residue at a time in a random decoding order, conditioned
+     on the structural encoding and previously sampled residues.
   4. **Temperature sampling**: The softmax temperature controls sequence
      diversity — lower temperatures produce sequences closer to the model's
      most confident prediction; higher temperatures increase diversity.
-  5. **Scoring**: Each designed sequence receives a negative log-likelihood
-     score (lower is better) and a sequence recovery metric measuring
-     similarity to the original sequence.
+  5. **Scoring**: Each designed sequence receives an average negative
+     log-likelihood score (always ≥ 0; lower is better) and a sequence
+     recovery metric measuring similarity to the original sequence.
 
 additional_context: |
-  - The **vanilla** model is trained on the full PDB and is the default choice
-    for most design tasks.
+  - The **vanilla** model is a backbone-atom model (N, Cα, C, O, virtual Cβ)
+    trained on PDB biological assemblies as of Aug 2021 (≤3.5 Å resolution,
+    <10,000 residues). It is the default choice for most design tasks.
   - The **soluble** model is trained only on soluble proteins and may produce
     sequences with better solubility characteristics.
-  - The **ca_only** model uses only C-alpha coordinates, useful when full
-    backbone atom positions are unavailable or unreliable.
-  - Lower sampling temperatures (0.1-0.3) produce more conservative, high-
-    confidence designs. Higher temperatures (0.5-1.0) increase diversity.
+  - The **ca_only** model uses only Cα coordinates, useful when full backbone
+    atom positions are unavailable or unreliable.
+  - Lower sampling temperatures (upstream recommends 0.1–0.3) produce more
+    conservative, high-confidence designs. Higher temperatures (0.5–1.0)
+    increase diversity but at T=1.0 sequences approach random.
   - Fixed residues are excluded from the design process entirely — their
     identity is held constant and used as context for designing other positions.
-  - Sequence recovery measures the fraction of designed residues that match the
-    original sequence. High recovery (~0.4-0.6) is typical for well-designed
-    backbones; very high recovery (>0.8) may indicate the backbone strongly
-    constrains the sequence space.
+  - Sequence recovery measures the fraction of designed residues that match
+    the original sequence. The paper reports ~52.4% mean recovery on native
+    backbones, so ~0.5 is the typical center for well-folded proteins; very
+    high recovery (>0.7) may indicate the backbone strongly constrains the
+    sequence space.
 
 # ─── Parameters ───
 # Parameter definitions are canonical here — keep in sync with proteinmpnn.py
@@ -101,9 +103,10 @@ parameters:
     default: vanilla
     description: |
       Model variant to use:
-      - **vanilla**: Full-atom model trained on the entire PDB (default)
+      - **vanilla**: Backbone-atom model (N, Cα, C, O, virtual Cβ) trained on
+        PDB biological assemblies as of Aug 2021, ≤3.5 Å (default)
       - **soluble**: Trained on soluble proteins only
-      - **ca_only**: Uses only C-alpha coordinates
+      - **ca_only**: Uses only Cα coordinates
 
   num-sequences:
     type: integer
@@ -115,11 +118,13 @@ parameters:
 
   temperature:
     type: float
-    default: 1.0
+    default: 0.1
     range: [0.01, 2.0]
     description: |
-      Sampling temperature controlling sequence diversity. Lower values
-      produce more conservative designs; higher values increase diversity.
+      Sampling temperature controlling sequence diversity. Upstream
+      ProteinMPNN's default and recommended range is 0.1–0.3; values
+      approaching 1.0 produce near-random sequences. Lower = more
+      conservative designs; higher = more diverse.
 
   seed:
     type: integer
@@ -169,14 +174,15 @@ output_metrics:
   best_score:
     display_name: Best Score
     description: |
-      **Best score** is the lowest (most favorable) negative log-likelihood
-      across all designed sequences. The score measures how well the designed
-      sequence fits the input backbone according to the ProteinMPNN model.
-      Lower values indicate higher model confidence that the sequence will
-      fold into the target structure.
+      **Best score** is the lowest (most favorable) average negative
+      log-likelihood across all designed sequences. The score measures how
+      well the designed sequence fits the input backbone according to the
+      ProteinMPNN model. The score is always ≥ 0 (since it is a NLL); lower
+      values indicate higher model confidence that the sequence will fold
+      into the target structure.
     interpretation: |
-      - Lower is better — there is no fixed scale
-      - Typical values range from roughly -3.0 to 0.0 depending on structure
+      - Lower is better; always positive
+      - Typical values per the upstream README examples are ~0.7–1.5
       - Compare across sequences within the same run for relative ranking
 
   mean_score:
@@ -198,8 +204,9 @@ output_metrics:
       designed positions, averaged across all generated sequences.
     range: [0, 1]
     interpretation: |
-      - 0.3–0.5: Typical for well-folded natural proteins
-      - >0.5: High recovery — backbone strongly constrains sequence space
+      - 0.4–0.55: Typical for well-folded native backbones (the paper reports
+        a 52.4% mean recovery)
+      - >0.6: High recovery — backbone strongly constrains sequence space
       - <0.3: Low recovery — backbone may accommodate diverse sequences
       - Very high recovery (>0.8) may indicate a rigid, highly constrained fold
 

{amina_cli-0.4.3 → amina_cli-0.5.1}/src/amina_cli/commands/tools/design/docs/rfdiffusion.yaml

@@ -47,7 +47,7 @@ tool_algorithm: |
   - **unconditional**: Base_ckpt.pt
   - **binder-design**: Complex_base_ckpt.pt (default), Complex_beta_ckpt.pt (diverse topologies)
   - **binder-redesign**: Base_ckpt.pt
-  - **motif-scaffolding**: Base_ckpt.pt, ActiveSite_ckpt.pt (small motifs), InpaintSeq_ckpt.pt
+  - **motif-scaffolding**: Base_ckpt.pt, ActiveSite_ckpt.pt (small motifs), InpaintSeq_ckpt.pt, InpaintSeq_Fold_ckpt.pt (when both inpaint_seq and fold_conditioning are set)
   - **partial-diffusion**: Base_ckpt.pt
   - **custom-contigs**: Any of 8 available checkpoints
 
@@ -60,9 +60,23 @@ additional_context: |
     binders but may have lower success rates.
   - Fold conditioning (--fold-conditioning) biases the diffusion toward specific
     fold topologies using PDB scaffold templates.
-  - Noise level for partial-diffusion and binder-redesign controls the degree of
-    structural diversification: lower noise (1-10) = subtle changes, higher noise
-    (25-50) = major backbone rearrangement.
+  - The `--noise` flag maps directly to RFdiffusion's `diffuser.partial_T`,
+    which is a discrete diffusion-timestep count (total `diffuser.T=50`).
+    Upstream guidance is `partial_T≈20` as a typical starting point; values
+    approaching T mean nearly full re-diffusion. Lower values stay closer to
+    the input backbone; higher values introduce more change.
+  - **binder-redesign accepts any input numbering.** Partial diffusion internally
+    requires each chain numbered contiguously from 1, but binder-redesign now
+    renumbers the input for you and restores the original chain IDs and residue
+    numbers on the output — so a target keeping its biological numbering (e.g.
+    residues 257-364) works as-is, and the output is returned with that numbering.
+  - **partial-diffusion still requires contiguous-from-1 numbering.** It maps input
+    residue positions directly onto the output, so every chain must be numbered
+    contiguously starting at residue 1 with no gaps; a chain starting at, say, 50
+    is rejected. Renumber first (e.g. the **PDB cleaner** tool, or `pdbtools`'
+    `pdb_reres`). This does not apply to
+    binder-design, which generates the binder de novo and references the target
+    as an explicit motif, so offset target numbering is fine there.
 
 # ─── Parameters ───
 # Parameter definitions are canonical here — keep in sync with rfdiffusion.py
@@ -85,6 +99,9 @@ parameters:
       Input PDB file. Required for binder-design, binder-redesign,
       motif-scaffolding, and partial-diffusion modes. Optional for
       custom-contigs.
+      For partial-diffusion, every chain must be numbered contiguously from
+      residue 1 (no gaps). binder-redesign handles any numbering automatically
+      (renumbered internally, restored on output) — see additional notes.
 
   num-designs:
     type: integer
@@ -109,8 +126,10 @@ parameters:
     required: false
     description: |
       Symmetry type for unconditional and motif-scaffolding modes.
-      Supports cyclic (c2, c3, c4...), dihedral (d2, d3...), and
-      tetrahedral symmetry.
+      Upstream RFdiffusion currently implements cyclic (c2, c3, c4…),
+      dihedral (d2, d3…), and tetrahedral symmetry. The schema validator
+      also accepts octahedral and icosahedral but upstream marks these
+      as "future".
     examples:
       - "c4"
       - "d2"
@@ -162,29 +181,38 @@ parameters:
     type: string
     required: false
     description: |
-      Target chain ID for binder-redesign mode. Defaults to 'B'.
+      Target chain ID(s) for binder-redesign mode. Defaults to 'B'. Accepts one
+      or more chains, comma-separated, to redesign the binder against a
+      multi-chain target. Each target chain is kept fixed during redesign.
     examples:
       - "B"
+      - "A,B"
 
   noise:
     type: integer
     required: false
     range: [1, 50]
     description: |
-      Noise level for partial-diffusion and binder-redesign modes.
-      Controls the degree of structural diversification. Lower values
-      (1-10) produce subtle changes; higher values (25-50) cause
-      major backbone rearrangement. Required for these modes.
+      Partial diffusion timestep count (maps to RFdiffusion's
+      `diffuser.partial_T`; total `diffuser.T=50`). Required for
+      partial-diffusion and binder-redesign modes. Upstream guidance is
+      `partial_T≈20` as a typical starting point — lower values stay
+      closer to the input backbone; values approaching 50 mean nearly
+      full re-diffusion.
 
   preserve:
     type: string
     required: false
     description: |
-      Residues to preserve during partial-diffusion and binder-redesign.
-      Comma-separated list of residue identifiers or ranges.
+      Residues whose sequence is preserved during partial-diffusion and
+      binder-redesign. Comma-separated list of residues or ranges, given as
+      PDB residue numbers. A chain-prefixed range (e.g. 'X10-25') targets that
+      chain; a bare range (e.g. '10-25') applies to the binder chain in
+      binder-redesign, or the first chain in partial-diffusion. These are
+      mapped internally to the contig positions RFdiffusion expects.
     examples:
-      - "10,20,30"
-      - "A10-25"
+      - "10-25"
+      - "X10-25,X40-50"
 
   contigs:
     type: string
@@ -259,6 +287,8 @@ examples:
     command: amina run rfdiffusion -m binder-design -i target.pdb --hotspots A30,A33 --binder-length 80-120 -o ./out/
   - title: Binder redesign
     command: amina run rfdiffusion -m binder-redesign -i complex.pdb --noise 25 --binder-chain A --target-chain B -o ./out/
+  - title: Binder redesign against a multi-chain target, preserving part of the binder
+    command: amina run rfdiffusion -m binder-redesign -i complex.pdb --noise 25 --binder-chain X --target-chain A,B --preserve X1-30 -o ./out/
   - title: Motif scaffolding
     command: amina run rfdiffusion -m motif-scaffolding -i motif.pdb --contigs "10-40/A163-181/10-40" -o ./out/
   - title: Partial diffusion
@@ -268,5 +298,7 @@ examples:
 
 # ─── References ───
 references:
-  - title: "RFDiffusion: De novo protein design by deep network hallucination (Watson et al., 2023)"
+  - title: "De novo design of protein structure and function with RFdiffusion (Watson et al., Nature 620, 1089–1100, 2023)"
+    url: "https://doi.org/10.1038/s41586-023-06415-8"
+  - title: "RFdiffusion GitHub source (RosettaCommons)"
     url: "https://github.com/RosettaCommons/RFdiffusion"

{amina_cli-0.4.3 → amina_cli-0.5.1}/src/amina_cli/commands/tools/design/proteinmpnn.py

@@ -52,9 +52,9 @@ def register(app: typer.Typer):
             help="Number of sequences to generate (1-50)",
         ),
         temperature: float = typer.Option(
-            1.0,
+            0.1,
             "--temperature",
-            help="Sampling temperature (0.01-2.0)",
+            help="Sampling temperature (0.01-2.0; upstream default 0.1, recommended 0.1-0.3)",
         ),
         seed: int = typer.Option(
             37,

{amina_cli-0.4.3 → amina_cli-0.5.1}/src/amina_cli/commands/tools/design/rfdiffusion.py

@@ -118,7 +118,7 @@ def register(app: typer.Typer):
             None,
             "--target-chain",
             "-tc",
-            help="Target chain ID (binder-redesign)",
+            help="Target chain ID(s) (binder-redesign). Comma-separate for multiple, e.g. 'A,B'",
         ),
         # Partial diffusion / redesign options
         noise_level: Optional[int] = typer.Option(
@@ -222,7 +222,8 @@ def register(app: typer.Typer):
                 raise typer.Exit(1)
             params["pdb_content"] = pdb_content
             params["binder_chain"] = binder_chain or "A"
-            params["target_chain"] = target_chain or "B"
+            # Accept one or more target chains, comma-separated (e.g. "A,B").
+            params["target_chain"] = [c.strip() for c in target_chain.split(",")] if target_chain else ["B"]
             params["noise_level"] = noise_level
             if preserve:
                 params["preserve_sequences"] = [p.strip() for p in preserve.split(",")]

{amina_cli-0.4.3 → amina_cli-0.5.1}/src/amina_cli/commands/tools/folding/boltz2.py

@@ -287,7 +287,7 @@ def register(app: typer.Typer):
             "recycling_steps": recycling_steps,
             "sampling_steps": sampling_steps,
             "diffusion_samples": diffusion_samples,
-            "step_scale": 1.638,
+            "step_scale": 1.5,
             "use_potentials": False,
             "enable_affinity_prediction": enable_affinity,
         }

{amina_cli-0.4.3 → amina_cli-0.5.1}/src/amina_cli/commands/tools/folding/docs/boltz2.yaml

@@ -19,7 +19,7 @@ when_to_use: |
   - Multi-chain protein complex modeling
   - Protein-nucleic acid (DNA/RNA) complex structures
   - When you need confidence metrics for predicted interfaces (ipTM, ipSAE)
-  - When binding affinity prediction (pKd) is needed alongside structure
+  - When binding affinity prediction (log10 IC50) is needed alongside structure
 
 when_not_to_use: |
   - Single-chain protein folding only → use **ESMFold** (faster, no MSA needed)
@@ -38,7 +38,7 @@ tool_algorithm: |
   1. **Input processing**: Sequences are tokenized; MSAs are generated or loaded;
      ligands are parsed from SMILES/CCD.
   2. **Trunk module**: Processes pairwise and MSA representations through
-     Evoformer-like attention blocks.
+     PairFormer attention blocks (PairformerArgsV2, 64 blocks).
   3. **Diffusion sampling**: Starting from noise, atom positions are refined
      over N denoising steps (default 200). More steps = finer detail.
   4. **Recycling**: The predicted structure is fed back through the trunk for
@@ -46,8 +46,9 @@ tool_algorithm: |
   5. **Confidence estimation**: PAE (Predicted Aligned Error), pLDDT, pTM, and
      ipTM are computed from internal representations. Additional metrics (ipSAE,
      LIS, pDockQ) are derived from the PAE matrix.
-  6. **Affinity prediction** (optional): A separate head predicts binding
-     affinity (pKd) for protein-ligand complexes.
+  6. **Affinity prediction** (optional): A separate PairFormer-based head
+     predicts a binary binding likelihood and an IC50-like affinity value
+     (log10 IC50 in μM) for protein–ligand complexes.
 
 additional_context: |
   - MSA generation adds ~60s to runtime for sequences without precomputed
@@ -157,8 +158,8 @@ parameters:
     type: boolean
     default: false
     description: |
-      Enable binding affinity prediction (pKd). Only works for
-      protein-ligand complexes — requires at least one `--ligand`.
+      Enable binding affinity prediction (log10 IC50 in μM). Only works
+      for protein-ligand complexes — requires at least one `--ligand`.
 
   job-name:
     type: string
@@ -199,9 +200,9 @@ output_metrics:
   ptm:
     display_name: pTM
     description: |
-      **pTM** (predicted TM-score) estimates the global fold quality of the
-      entire predicted structure. Derived from the PAE matrix, measuring
-      overall structural similarity to the ground truth.
+      **pTM** (predicted TM-score) is the model's estimate of the TM-score its
+      structure would achieve against ground truth, using only the model's own
+      PAE matrix (no ground-truth structure is available at inference).
     range: [0, 1]
     interpretation: |
       - >0.8: High-quality global fold prediction
@@ -224,8 +225,9 @@ output_metrics:
   confidence_score:
     display_name: Confidence Score
     description: |
-      Combined confidence metric computed as `0.2 * ipTM + 0.8 * pTM`.
-      Gives a single overall quality score weighted toward global fold quality.
+      Aggregated ranking score used by Boltz-2 to order samples. Computed as
+      `0.8 * complex_plddt + 0.2 * ipTM` (Boltz-2 falls back to `0.8 * pLDDT
+      + 0.2 * pTM` when there are no interfaces). Weighted toward pLDDT.
     range: [0, 1]
     interpretation: |
       - >0.8: High overall prediction confidence
@@ -274,44 +276,52 @@ output_metrics:
   lis:
     display_name: LIS
     description: |
-      **LIS** (Local Interface Score) evaluates interface quality using
-      local PAE values between interface residue pairs. Focuses on nearby
-      contacts rather than global alignment.
+      **LIS** (Local Interaction Score) evaluates protein-protein interaction
+      quality from inverted PAE values within the local interaction area
+      (residue pairs with PAE ≤ 12 Å). Introduced by Kim et al. 2024
+      (bioRxiv 2024.02.19.580970).
     range: [0, 1]
     interpretation: |
-      - >0.5: Good interface contacts predicted
-      - <0.5: Weak interface prediction
+      - Higher is better; AFM-LIS benchmarks Best LIS ≥ 0.203 / Average LIS
+        ≥ 0.073 as positive-call thresholds.
 
   pdockq:
     display_name: pDockQ
     description: |
       **pDockQ** (predicted DockQ) estimates the quality of a predicted
       protein-protein docked complex, calibrated against the DockQ benchmark.
-      Computed from the number of interface contacts and average interface pLDDT.
+      Bryant et al. 2022 define it as a sigmoidal fit on `average interface
+      pLDDT × log(interface contacts)`.
     range: [0, 1]
     interpretation: |
-      - >0.5: Acceptable docking quality
-      - >0.23: Possible interaction
-      - <0.23: Unlikely to be a correct docked pose
+      - >0.5: confidently predicted interface
+      - 0.23–0.5: borderline (pDockQ is noisy in this range; 0.23 is the
+        DockQ-acceptable calibration target, not a pDockQ cutoff)
+      - <0.23: unlikely interaction
 
   pdockq2:
     display_name: pDockQ2
     description: |
-      **pDockQ2** is an improved version of pDockQ that uses a multi-model
-      scoring approach for better discrimination of correct interfaces.
+      **pDockQ2** augments pDockQ by incorporating the predicted aligned
+      error (PAE) between chains, giving better calibration on multimers
+      and homomers where pDockQ can over-score large but incorrect
+      interfaces (Zhu et al. 2023, Bioinformatics btad424).
     range: [0, 1]
     interpretation: |
-      - Higher is better; interpretation similar to pDockQ
+      - Higher is better; interpretation similar to pDockQ.
 
   affinity_pred_value:
-    display_name: Predicted pKd
+    display_name: log10(IC50, μM)
     description: |
-      Predicted binding affinity as pKd (negative log of dissociation constant).
-      Only available when `--affinity` is enabled for protein-ligand complexes.
+      Predicted binding affinity as `log10(IC50)` with IC50 in μM. Lower
+      values indicate stronger binding (e.g., −3 ≈ 1 nM, 0 ≈ 1 μM, 2 ≈
+      100 μM weak/decoy). Only available when `--affinity` is enabled for
+      protein–ligand complexes.
     interpretation: |
-      - Higher pKd = tighter binding (e.g., pKd 9 = 1 nM Kd)
-      - Typical drug-like: pKd 6–10
-      - Weak binder: pKd < 5
+      - Lower = tighter binding
+      - −3 to −1: strong binder (≈ 1 nM – 100 nM)
+      - −1 to 1: moderate (≈ 100 nM – 10 μM)
+      - >1: weak / non-binder
 
   affinity_probability_binary:
     display_name: Binding Probability
@@ -378,7 +388,7 @@ output_display:
     - title: Binding Affinity Prediction
       fields:
         - key: affinity_pred_value
-          label: Predicted pKd
+          label: log10(IC50, μM)
         - key: affinity_probability_binary
           label: Binding Probability
 
@@ -397,5 +407,15 @@ examples:
 
 # ─── References ───
 references:
-  - title: "Boltz-2: Biomolecular Interaction Modeling"
+  - title: "Boltz-2: Jointly Modeling Structure and Binding Affinity (Passaro et al., 2025)"
+    url: "https://doi.org/10.1101/2025.06.14.659707"
+  - title: "Boltz GitHub source"
     url: "https://github.com/jwohlwend/boltz"
+  - title: "ipSAE — Interaction prediction Score from Aligned Errors (Dunbrack 2025)"
+    url: "https://www.biorxiv.org/content/10.1101/2025.02.10.637595v1"
+  - title: "LIS — Local Interaction Score (Kim et al. 2024)"
+    url: "https://www.biorxiv.org/content/10.1101/2024.02.19.580970v1"
+  - title: "pDockQ (Bryant et al., Nat Commun 2022)"
+    url: "https://www.nature.com/articles/s41467-022-28865-w"
+  - title: "pDockQ2 (Zhu et al., Bioinformatics 2023, btad424)"
+    url: "https://academic.oup.com/bioinformatics/article/39/7/btad424/7219714"