boltz-vsynthes 1.0.0__py3-none-any.whl

boltz/model/loss/confidence.py

@@ -0,0 +1,590 @@
+import torch
+from torch import nn
+
+from boltz.data import const
+
+
+def confidence_loss(
+    model_out,
+    feats,
+    true_coords,
+    true_coords_resolved_mask,
+    multiplicity=1,
+    alpha_pae=0.0,
+):
+    """Compute confidence loss.
+
+    Parameters
+    ----------
+    model_out: Dict[str, torch.Tensor]
+        Dictionary containing the model output
+    feats: Dict[str, torch.Tensor]
+        Dictionary containing the model input
+    true_coords: torch.Tensor
+        The atom coordinates after symmetry correction
+    true_coords_resolved_mask: torch.Tensor
+        The resolved mask after symmetry correction
+    multiplicity: int, optional
+        The diffusion batch size, by default 1
+    alpha_pae: float, optional
+        The weight of the pae loss, by default 0.0
+
+    Returns
+    -------
+    Dict[str, torch.Tensor]
+        Loss breakdown
+
+    """
+    # Compute losses
+    plddt = plddt_loss(
+        model_out["plddt_logits"],
+        model_out["sample_atom_coords"],
+        true_coords,
+        true_coords_resolved_mask,
+        feats,
+        multiplicity=multiplicity,
+    )
+    pde = pde_loss(
+        model_out["pde_logits"],
+        model_out["sample_atom_coords"],
+        true_coords,
+        true_coords_resolved_mask,
+        feats,
+        multiplicity,
+    )
+    resolved = resolved_loss(
+        model_out["resolved_logits"],
+        feats,
+        true_coords_resolved_mask,
+        multiplicity=multiplicity,
+    )
+
+    pae = 0.0
+    if alpha_pae > 0.0:
+        pae = pae_loss(
+            model_out["pae_logits"],
+            model_out["sample_atom_coords"],
+            true_coords,
+            true_coords_resolved_mask,
+            feats,
+            multiplicity,
+        )
+
+    loss = plddt + pde + resolved + alpha_pae * pae
+
+    dict_out = {
+        "loss": loss,
+        "loss_breakdown": {
+            "plddt_loss": plddt,
+            "pde_loss": pde,
+            "resolved_loss": resolved,
+            "pae_loss": pae,
+        },
+    }
+    return dict_out
+
+
+def resolved_loss(
+    pred_resolved,
+    feats,
+    true_coords_resolved_mask,
+    multiplicity=1,
+):
+    """Compute resolved loss.
+
+    Parameters
+    ----------
+    pred_resolved: torch.Tensor
+        The resolved logits
+    feats: Dict[str, torch.Tensor]
+        Dictionary containing the model input
+    true_coords_resolved_mask: torch.Tensor
+        The resolved mask after symmetry correction
+    multiplicity: int, optional
+        The diffusion batch size, by default 1
+
+    Returns
+    -------
+    torch.Tensor
+        Resolved loss
+
+    """
+
+    # extract necessary features
+    token_to_rep_atom = feats["token_to_rep_atom"]
+    token_to_rep_atom = token_to_rep_atom.repeat_interleave(multiplicity, 0).float()
+    ref_mask = torch.bmm(
+        token_to_rep_atom, true_coords_resolved_mask.unsqueeze(-1).float()
+    ).squeeze(-1)
+    pad_mask = feats["token_pad_mask"]
+    pad_mask = pad_mask.repeat_interleave(multiplicity, 0).float()
+
+    # compute loss
+    log_softmax_resolved = torch.nn.functional.log_softmax(pred_resolved, dim=-1)
+    errors = (
+        -ref_mask * log_softmax_resolved[:, :, 0]
+        - (1 - ref_mask) * log_softmax_resolved[:, :, 1]
+    )
+    loss = torch.sum(errors * pad_mask, dim=-1) / (1e-7 + torch.sum(pad_mask, dim=-1))
+
+    # Average over the batch dimension
+    loss = torch.mean(loss)
+
+    return loss
+
+
+def plddt_loss(
+    pred_lddt,
+    pred_atom_coords,
+    true_atom_coords,
+    true_coords_resolved_mask,
+    feats,
+    multiplicity=1,
+):
+    """Compute plddt loss.
+
+    Parameters
+    ----------
+    pred_lddt: torch.Tensor
+        The plddt logits
+    pred_atom_coords: torch.Tensor
+        The predicted atom coordinates
+    true_atom_coords: torch.Tensor
+        The atom coordinates after symmetry correction
+    true_coords_resolved_mask: torch.Tensor
+        The resolved mask after symmetry correction
+    feats: Dict[str, torch.Tensor]
+        Dictionary containing the model input
+    multiplicity: int, optional
+        The diffusion batch size, by default 1
+
+    Returns
+    -------
+    torch.Tensor
+        Plddt loss
+
+    """
+
+    # extract necessary features
+    atom_mask = true_coords_resolved_mask
+
+    R_set_to_rep_atom = feats["r_set_to_rep_atom"]
+    R_set_to_rep_atom = R_set_to_rep_atom.repeat_interleave(multiplicity, 0).float()
+
+    token_type = feats["mol_type"]
+    token_type = token_type.repeat_interleave(multiplicity, 0)
+    is_nucleotide_token = (token_type == const.chain_type_ids["DNA"]).float() + (
+        token_type == const.chain_type_ids["RNA"]
+    ).float()
+
+    B = true_atom_coords.shape[0]
+
+    atom_to_token = feats["atom_to_token"].float()
+    atom_to_token = atom_to_token.repeat_interleave(multiplicity, 0)
+
+    token_to_rep_atom = feats["token_to_rep_atom"].float()
+    token_to_rep_atom = token_to_rep_atom.repeat_interleave(multiplicity, 0)
+
+    true_token_coords = torch.bmm(token_to_rep_atom, true_atom_coords)
+    pred_token_coords = torch.bmm(token_to_rep_atom, pred_atom_coords)
+
+    # compute true lddt
+    true_d = torch.cdist(
+        true_token_coords,
+        torch.bmm(R_set_to_rep_atom, true_atom_coords),
+    )
+    pred_d = torch.cdist(
+        pred_token_coords,
+        torch.bmm(R_set_to_rep_atom, pred_atom_coords),
+    )
+
+    # compute mask
+    pair_mask = atom_mask.unsqueeze(-1) * atom_mask.unsqueeze(-2)
+    pair_mask = (
+        pair_mask
+        * (1 - torch.eye(pair_mask.shape[1], device=pair_mask.device))[None, :, :]
+    )
+    pair_mask = torch.einsum("bnm,bkm->bnk", pair_mask, R_set_to_rep_atom)
+    pair_mask = torch.bmm(token_to_rep_atom, pair_mask)
+    atom_mask = torch.bmm(token_to_rep_atom, atom_mask.unsqueeze(-1).float())
+    is_nucleotide_R_element = torch.bmm(
+        R_set_to_rep_atom, torch.bmm(atom_to_token, is_nucleotide_token.unsqueeze(-1))
+    ).squeeze(-1)
+    cutoff = 15 + 15 * is_nucleotide_R_element.reshape(B, 1, -1).repeat(
+        1, true_d.shape[1], 1
+    )
+
+    # compute lddt
+    target_lddt, mask_no_match = lddt_dist(
+        pred_d, true_d, pair_mask, cutoff, per_atom=True
+    )
+
+    # compute loss
+    num_bins = pred_lddt.shape[-1]
+    bin_index = torch.floor(target_lddt * num_bins).long()
+    bin_index = torch.clamp(bin_index, max=(num_bins - 1))
+    lddt_one_hot = nn.functional.one_hot(bin_index, num_classes=num_bins)
+    errors = -1 * torch.sum(
+        lddt_one_hot * torch.nn.functional.log_softmax(pred_lddt, dim=-1),
+        dim=-1,
+    )
+    atom_mask = atom_mask.squeeze(-1)
+    loss = torch.sum(errors * atom_mask * mask_no_match, dim=-1) / (
+        1e-7 + torch.sum(atom_mask * mask_no_match, dim=-1)
+    )
+
+    # Average over the batch dimension
+    loss = torch.mean(loss)
+
+    return loss
+
+
+def pde_loss(
+    pred_pde,
+    pred_atom_coords,
+    true_atom_coords,
+    true_coords_resolved_mask,
+    feats,
+    multiplicity=1,
+    max_dist=32.0,
+):
+    """Compute pde loss.
+
+    Parameters
+    ----------
+    pred_pde: torch.Tensor
+        The pde logits
+    pred_atom_coords: torch.Tensor
+        The predicted atom coordinates
+    true_atom_coords: torch.Tensor
+        The atom coordinates after symmetry correction
+    true_coords_resolved_mask: torch.Tensor
+        The resolved mask after symmetry correction
+    feats: Dict[str, torch.Tensor]
+        Dictionary containing the model input
+    multiplicity: int, optional
+        The diffusion batch size, by default 1
+
+    Returns
+    -------
+    torch.Tensor
+        Pde loss
+
+    """
+
+    # extract necessary features
+    token_to_rep_atom = feats["token_to_rep_atom"]
+    token_to_rep_atom = token_to_rep_atom.repeat_interleave(multiplicity, 0).float()
+    token_mask = torch.bmm(
+        token_to_rep_atom, true_coords_resolved_mask.unsqueeze(-1).float()
+    ).squeeze(-1)
+    mask = token_mask.unsqueeze(-1) * token_mask.unsqueeze(-2)
+
+    # compute true pde
+    true_token_coords = torch.bmm(token_to_rep_atom, true_atom_coords)
+    pred_token_coords = torch.bmm(token_to_rep_atom, pred_atom_coords)
+
+    true_d = torch.cdist(true_token_coords, true_token_coords)
+    pred_d = torch.cdist(pred_token_coords, pred_token_coords)
+    target_pde = torch.abs(true_d - pred_d)
+
+    # compute loss
+    num_bins = pred_pde.shape[-1]
+    bin_index = torch.floor(target_pde * num_bins / max_dist).long()
+    bin_index = torch.clamp(bin_index, max=(num_bins - 1))
+    pde_one_hot = nn.functional.one_hot(bin_index, num_classes=num_bins)
+    errors = -1 * torch.sum(
+        pde_one_hot * torch.nn.functional.log_softmax(pred_pde, dim=-1),
+        dim=-1,
+    )
+    loss = torch.sum(errors * mask, dim=(-2, -1)) / (
+        1e-7 + torch.sum(mask, dim=(-2, -1))
+    )
+
+    # Average over the batch dimension
+    loss = torch.mean(loss)
+
+    return loss
+
+
+def pae_loss(
+    pred_pae,
+    pred_atom_coords,
+    true_atom_coords,
+    true_coords_resolved_mask,
+    feats,
+    multiplicity=1,
+    max_dist=32.0,
+):
+    """Compute pae loss.
+
+    Parameters
+    ----------
+    pred_pae: torch.Tensor
+        The pae logits
+    pred_atom_coords: torch.Tensor
+        The predicted atom coordinates
+    true_atom_coords: torch.Tensor
+        The atom coordinates after symmetry correction
+    true_coords_resolved_mask: torch.Tensor
+        The resolved mask after symmetry correction
+    feats: Dict[str, torch.Tensor]
+        Dictionary containing the model input
+    multiplicity: int, optional
+        The diffusion batch size, by default 1
+
+    Returns
+    -------
+    torch.Tensor
+        Pae loss
+
+    """
+    # Retrieve frames and resolved masks
+    frames_idx_original = feats["frames_idx"]
+    mask_frame_true = feats["frame_resolved_mask"]
+
+    # Adjust the frames for nonpolymers after symmetry correction!
+    # NOTE: frames of polymers do not change under symmetry!
+    frames_idx_true, mask_collinear_true = compute_frame_pred(
+        true_atom_coords,
+        frames_idx_original,
+        feats,
+        multiplicity,
+        resolved_mask=true_coords_resolved_mask,
+    )
+
+    frame_true_atom_a, frame_true_atom_b, frame_true_atom_c = (
+        frames_idx_true[:, :, :, 0],
+        frames_idx_true[:, :, :, 1],
+        frames_idx_true[:, :, :, 2],
+    )
+    # Compute token coords in true frames
+    B, N, _ = true_atom_coords.shape
+    true_atom_coords = true_atom_coords.reshape(B // multiplicity, multiplicity, -1, 3)
+    true_coords_transformed = express_coordinate_in_frame(
+        true_atom_coords, frame_true_atom_a, frame_true_atom_b, frame_true_atom_c
+    )
+
+    # Compute pred frames and mask
+    frames_idx_pred, mask_collinear_pred = compute_frame_pred(
+        pred_atom_coords, frames_idx_original, feats, multiplicity
+    )
+    frame_pred_atom_a, frame_pred_atom_b, frame_pred_atom_c = (
+        frames_idx_pred[:, :, :, 0],
+        frames_idx_pred[:, :, :, 1],
+        frames_idx_pred[:, :, :, 2],
+    )
+    # Compute token coords in pred frames
+    B, N, _ = pred_atom_coords.shape
+    pred_atom_coords = pred_atom_coords.reshape(B // multiplicity, multiplicity, -1, 3)
+    pred_coords_transformed = express_coordinate_in_frame(
+        pred_atom_coords, frame_pred_atom_a, frame_pred_atom_b, frame_pred_atom_c
+    )
+
+    target_pae = torch.sqrt(
+        ((true_coords_transformed - pred_coords_transformed) ** 2).sum(-1) + 1e-8
+    )
+
+    # Compute mask for the pae loss
+    b_true_resolved_mask = true_coords_resolved_mask[
+        torch.arange(B // multiplicity)[:, None, None].to(
+            pred_coords_transformed.device
+        ),
+        frame_true_atom_b,
+    ]
+
+    pair_mask = (
+        mask_frame_true[:, None, :, None]  # if true frame is invalid
+        * mask_collinear_true[:, :, :, None]  # if true frame is invalid
+        * mask_collinear_pred[:, :, :, None]  # if pred frame is invalid
+        * b_true_resolved_mask[:, :, None, :]  # If atom j is not resolved
+        * feats["token_pad_mask"][:, None, :, None]
+        * feats["token_pad_mask"][:, None, None, :]
+    )
+
+    # compute loss
+    num_bins = pred_pae.shape[-1]
+    bin_index = torch.floor(target_pae * num_bins / max_dist).long()
+    bin_index = torch.clamp(bin_index, max=(num_bins - 1))
+    pae_one_hot = nn.functional.one_hot(bin_index, num_classes=num_bins)
+    errors = -1 * torch.sum(
+        pae_one_hot
+        * torch.nn.functional.log_softmax(pred_pae.reshape(pae_one_hot.shape), dim=-1),
+        dim=-1,
+    )
+    loss = torch.sum(errors * pair_mask, dim=(-2, -1)) / (
+        1e-7 + torch.sum(pair_mask, dim=(-2, -1))
+    )
+    # Average over the batch dimension
+    loss = torch.mean(loss)
+
+    return loss
+
+
+def lddt_dist(dmat_predicted, dmat_true, mask, cutoff=15.0, per_atom=False):
+    # NOTE: the mask is a pairwise mask which should have the identity elements already masked out
+    # Compute mask over distances
+    dists_to_score = (dmat_true < cutoff).float() * mask
+    dist_l1 = torch.abs(dmat_true - dmat_predicted)
+
+    score = 0.25 * (
+        (dist_l1 < 0.5).float()
+        + (dist_l1 < 1.0).float()
+        + (dist_l1 < 2.0).float()
+        + (dist_l1 < 4.0).float()
+    )
+
+    # Normalize over the appropriate axes.
+    if per_atom:
+        mask_no_match = torch.sum(dists_to_score, dim=-1) != 0
+        norm = 1.0 / (1e-10 + torch.sum(dists_to_score, dim=-1))
+        score = norm * (1e-10 + torch.sum(dists_to_score * score, dim=-1))
+        return score, mask_no_match.float()
+    else:
+        norm = 1.0 / (1e-10 + torch.sum(dists_to_score, dim=(-2, -1)))
+        score = norm * (1e-10 + torch.sum(dists_to_score * score, dim=(-2, -1)))
+        total = torch.sum(dists_to_score, dim=(-1, -2))
+        return score, total
+
+
+def express_coordinate_in_frame(atom_coords, frame_atom_a, frame_atom_b, frame_atom_c):
+    batch, multiplicity = atom_coords.shape[0], atom_coords.shape[1]
+    batch_indices0 = torch.arange(batch)[:, None, None].to(atom_coords.device)
+    batch_indices1 = torch.arange(multiplicity)[None, :, None].to(atom_coords.device)
+
+    # extract frame atoms
+    a, b, c = (
+        atom_coords[batch_indices0, batch_indices1, frame_atom_a],
+        atom_coords[batch_indices0, batch_indices1, frame_atom_b],
+        atom_coords[batch_indices0, batch_indices1, frame_atom_c],
+    )
+    w1 = (a - b) / (torch.norm(a - b, dim=-1, keepdim=True) + 1e-5)
+    w2 = (c - b) / (torch.norm(c - b, dim=-1, keepdim=True) + 1e-5)
+
+    # build orthogonal frame
+    e1 = (w1 + w2) / (torch.norm(w1 + w2, dim=-1, keepdim=True) + 1e-5)
+    e2 = (w2 - w1) / (torch.norm(w2 - w1, dim=-1, keepdim=True) + 1e-5)
+    e3 = torch.linalg.cross(e1, e2)
+
+    # project onto frame basis
+    d = b[:, :, None, :, :] - b[:, :, :, None, :]
+    x_transformed = torch.cat(
+        [
+            torch.sum(d * e1[:, :, :, None, :], dim=-1, keepdim=True),
+            torch.sum(d * e2[:, :, :, None, :], dim=-1, keepdim=True),
+            torch.sum(d * e3[:, :, :, None, :], dim=-1, keepdim=True),
+        ],
+        dim=-1,
+    )
+    return x_transformed
+
+
+def compute_collinear_mask(v1, v2):
+    # Compute the mask for collinear or overlapping atoms
+    norm1 = torch.norm(v1, dim=1, keepdim=True)
+    norm2 = torch.norm(v2, dim=1, keepdim=True)
+    v1 = v1 / (norm1 + 1e-6)
+    v2 = v2 / (norm2 + 1e-6)
+    mask_angle = torch.abs(torch.sum(v1 * v2, dim=1)) < 0.9063
+    mask_overlap1 = norm1.reshape(-1) > 1e-2
+    mask_overlap2 = norm2.reshape(-1) > 1e-2
+    return mask_angle & mask_overlap1 & mask_overlap2
+
+
+def compute_frame_pred(
+    pred_atom_coords,
+    frames_idx_true,
+    feats,
+    multiplicity,
+    resolved_mask=None,
+    inference=False,
+):
+    # extract necessary features
+    asym_id_token = feats["asym_id"]
+    asym_id_atom = torch.bmm(
+        feats["atom_to_token"].float(), asym_id_token.unsqueeze(-1).float()
+    ).squeeze(-1)
+    B, N, _ = pred_atom_coords.shape
+    pred_atom_coords = pred_atom_coords.reshape(B // multiplicity, multiplicity, -1, 3)
+    frames_idx_pred = (
+        frames_idx_true.clone()
+        .repeat_interleave(multiplicity, 0)
+        .reshape(B // multiplicity, multiplicity, -1, 3)
+    )
+
+    # Iterate through the batch and update the frames for nonpolymers
+    for i, pred_atom_coord in enumerate(pred_atom_coords):
+        token_idx = 0
+        atom_idx = 0
+        for id in torch.unique(asym_id_token[i]):
+            mask_chain_token = (asym_id_token[i] == id) * feats["token_pad_mask"][i]
+            mask_chain_atom = (asym_id_atom[i] == id) * feats["atom_pad_mask"][i]
+            num_tokens = int(mask_chain_token.sum().item())
+            num_atoms = int(mask_chain_atom.sum().item())
+            if (
+                feats["mol_type"][i, token_idx] != const.chain_type_ids["NONPOLYMER"]
+                or num_atoms < 3
+            ):
+                token_idx += num_tokens
+                atom_idx += num_atoms
+                continue
+            dist_mat = (
+                (
+                    pred_atom_coord[:, mask_chain_atom.bool()][:, None, :, :]
+                    - pred_atom_coord[:, mask_chain_atom.bool()][:, :, None, :]
+                )
+                ** 2
+            ).sum(-1) ** 0.5
+
+            # Sort the atoms by distance
+            if inference:
+                resolved_pair = 1 - (
+                    feats["atom_pad_mask"][i][mask_chain_atom.bool()][None, :]
+                    * feats["atom_pad_mask"][i][mask_chain_atom.bool()][:, None]
+                ).to(torch.float32)
+                resolved_pair[resolved_pair == 1] = torch.inf
+                indices = torch.sort(dist_mat + resolved_pair, axis=2).indices
+            else:
+                if resolved_mask is None:
+                    resolved_mask = feats["atom_resolved_mask"]
+                resolved_pair = 1 - (
+                    resolved_mask[i][mask_chain_atom.bool()][None, :]
+                    * resolved_mask[i][mask_chain_atom.bool()][:, None]
+                ).to(torch.float32)
+                resolved_pair[resolved_pair == 1] = torch.inf
+                indices = torch.sort(dist_mat + resolved_pair, axis=2).indices
+
+            # Compute the frames
+            frames = (
+                torch.cat(
+                    [
+                        indices[:, :, 1:2],
+                        indices[:, :, 0:1],
+                        indices[:, :, 2:3],
+                    ],
+                    dim=2,
+                )
+                + atom_idx
+            )
+            frames_idx_pred[i, :, token_idx : token_idx + num_atoms, :] = frames
+            token_idx += num_tokens
+            atom_idx += num_atoms
+
+    # Expand the frames with the multiplicity
+    frames_expanded = pred_atom_coords[
+        torch.arange(0, B // multiplicity, 1)[:, None, None, None].to(
+            frames_idx_pred.device
+        ),
+        torch.arange(0, multiplicity, 1)[None, :, None, None].to(
+            frames_idx_pred.device
+        ),
+        frames_idx_pred,
+    ].reshape(-1, 3, 3)
+
+    # Compute masks for collinear or overlapping atoms in the frame
+    mask_collinear_pred = compute_collinear_mask(
+        frames_expanded[:, 1] - frames_expanded[:, 0],
+        frames_expanded[:, 1] - frames_expanded[:, 2],
+    ).reshape(B // multiplicity, multiplicity, -1)
+
+    return frames_idx_pred, mask_collinear_pred * feats["token_pad_mask"][:, None, :]