work dump, add onnx stuff

README.md

 
-# Lead Optimization via Fragment Prediction
+# Lead Optimization
 
-# Overview
+# Structure
 
 - `config`: configuration information (eg. TRAIN/TEST partitions)
 - `data`: training/inference data (see [`data/README.md`](data/README.md))

launch.py

+
+import argparse
+import sys
+import os
+import subprocess
+import tempfile
+
+
+RUN_DIR = '/zfs1/jdurrant/durrantlab/hag63/leadopt_pytorch'
+
+
+def main():
+    parser = argparse.ArgumentParser()
+
+    parser.add_argument('-t','--time',default='10:00:00')
+    parser.add_argument('-p','--partition',default='gtx1080')
+    parser.add_argument('-m','--mem',default='16g')
+    parser.add_argument('path')
+    parser.add_argument('script')
+    
+    args = parser.parse_args()
+
+    run_path = os.path.join(RUN_DIR, args.path)
+    if os.path.exists(run_path):
+        print('[!] Run exists at %s' % run_path)
+        overwrite = input('- Overwrite? [Y/n]: ')
+        if overwrite.lower() == 'n':
+            print('Exiting...')
+            exit(0)
+    else:
+        print('[*] Creating run directory %s' % run_path)
+        os.mkdir(run_path)
+    
+    script = '''#!/bin/bash
+#SBATCH --job-name={name}
+#SBATCH --output={run_path}/slurm_out.txt
+#SBATCH --error={run_path}/slurm_err.txt
+#SBATCH --time={time}
+#SBATCH --nodes=1
+#SBATCH --ntasks=1
+#SBATCH --cluster=gpu
+#SBATCH --partition={partition}
+#SBATCH --mail-user=hag63@pitt.edu
+#SBATCH --mail-type=END,FAIL
+#SBATCH --gres=gpu:1
+#SBATCH --mem={mem}
+
+cd /ihome/jdurrant/hag63/cbio/leadopt_pytorch/
+./setup.sh
+
+export PYTHONPATH=/ihome/jdurrant/hag63/cbio/leadopt_pytorch/
+# export WANDB_DIR=/ihome/jdurrant/hag63/wandb_abs
+export WANDB_DISABLE_CODE=true
+
+cd {run_path}
+python /ihome/jdurrant/hag63/cbio/leadopt_pytorch/{script}
+    '''.format(
+        name='leadopt_%s' % args.path,
+        run_path=run_path,
+        time=args.time,
+        partition=args.partition,
+        mem=args.mem,
+        script=args.script
+    )
+
+    print('[*] Running script...')
+    
+    with tempfile.NamedTemporaryFile('w') as f:
+        f.write(script)
+        f.flush()
+        
+        r = subprocess.run('sbatch %s' % f.name, shell=True, stdin=subprocess.PIPE, stdout=subprocess.PIPE)
+        print(r)
+
+
+
+if __name__=='__main__':
+    main()

launch.sh

+#!/bin/bash
+
+DEFAULT_RUN_PATH=/zfs1/jdurrant/durrantlab/hag63/leadopt_pytorch/
+
+if [[ $# -ne 4 ]]; then
+    echo "Usage: $0 <run_name> <gpu_partition> <**args>"
+    exit 0
+fi
+
+ABS_SCRIPT=$(pwd)/train.py
+
+# navigate to runs directory
+RUNS_DIR="${RUNS_DIR:-$DEFAULT_RUN_PATH}"
+cd $RUNS_DIR
+
+if [[ -d $1 ]]; then
+    echo "Warning: run directory $1 already exists!"
+    exit -1
+fi
+
+echo "Creating run directory ($1)..."
+mkdir $1
+
+echo "Running script..."
+sbatch <<EOT
+#!/bin/bash
+#SBATCH --job-name=$1
+#SBATCH --output=$RUNS_DIR/$1/slurm_out.txt
+#SBATCH --error=$RUNS_DIR/$1/slurm_err.txt
+#SBATCH --time=10:00:00
+#SBATCH --nodes=1
+#SBATCH --ntasks=1
+#SBATCH --cluster=gpu
+#SBATCH --partition=$2
+#SBATCH --mail-user=hag63@pitt.edu
+#SBATCH --mail-type=END,FAIL
+#SBATCH --gres=gpu:1
+#SBATCH --mem=80g
+
+cd /ihome/jdurrant/hag63/cbio/leadopt_pytorch/
+source ./setup.sh
+
+PYTHON_PATH=$PYTHON_PATH:/ihome/jdurrant/hag63/cbio/leadopt_pytorch/
+
+cd $RUNS_DIR/$1
+python train.py $4
+EOT

leadopt.py

@@ -13,52 +13,9 @@ import h5py
 
 from leadopt.models.voxel import VoxelFingerprintNet2
 from leadopt.infer import infer_all
+from leadopt.pretrained import MODELS
 
 
-class SavedModel(object):
-    
-    model_class = None
-    model_args = None
-    
-    @classmethod
-    def load(cls, path):
-        m = cls.model_class(**cls.model_args).cuda()
-        m.load_state_dict(torch.load(path))
-        m.eval()
-        return m
-    
-    @classmethod
-    def get_fingerprints(cls, path):
-        f = h5py.File(os.path.join(path, cls.fingerprint_data), 'r')
-        
-        data = f['fingerprints'][()]
-        smiles = f['smiles'][()]
-        
-        f.close()
-        
-        return data, smiles
-    
-class V2_RDK_M150(SavedModel):
-    model_class = VoxelFingerprintNet2
-    model_args = {
-        'in_channels': 18,
-        'output_size': 2048,
-        'batchnorm': True,
-        'sigmoid': True
-    }
-    
-    grid_width=24
-    grid_res=1
-    receptor_types=[6,7,8,9,15,16,17,35,53]
-    parent_types=[6,7,8,9,15,16,17,35,53]
-    
-    fingerprint_data = 'fingerprint_rdk_2048.h5'
-
-
-MODELS = {
-    'rdk_m150': V2_RDK_M150
-}
-
 def main():
     parser = argparse.ArgumentParser()
 

leadopt/data_util.py

@@ -8,28 +8,161 @@ import os
 from torch.utils.data import DataLoader, Dataset
 import numpy as np
 import h5py
+import tqdm
 
 
-# Default atomic numbers to use as grid layers
-DEFAULT_TYPES = [6,7,8,9,15,16,17,35,53]
 
 
-def remap_atoms(atom_types):
-    '''
-    Returns a function that maps an atomic number to layer index.
+def rec_typer_single(t):
+    '''single channel no hydrogen'''
+    # unpack features
+    num, hacc, hdon, aro, _ = t
+    
+    if num != 1:
+        return 0
+    else:
+        return -1
+    
+def rec_typer_single_h(t):
+    '''single channel with hydrogen'''
+    # unpack features
+    return 0
+    
+def rec_typer_basic(t):
+    '''simple types'''
+    BASIC_TYPES = [6,7,8,16]
+    num, hacc, hdon, aro, _ = t
+    
+    if num in BASIC_TYPES:
+        return BASIC_TYPES.index(num)
+    else:
+        return -1
+    
+def rec_typer_basic_h(t):
+    '''simple types with hydrogen'''
+    BASIC_TYPES = [1,6,7,8,16]
+    num, hacc, hdon, aro, _ = t
+    
+    if num in BASIC_TYPES:
+        return BASIC_TYPES.index(num)
+    else:
+        return -1
 
-    Params:
-    - atom_types: which atom types to use as layers
-    '''
-    atom_mapping = {atom_types[i]:i for i in range(len(atom_types))}
+# aro, hdon, hacc
+REC_DESC = [
+    (6,0,0,0), # C
+    (6,1,0,0), # C-aro
+    (7,0,0,0), # N
+    (7,0,0,1), # N-hacc
+    (7,0,1,0), # N-hdon
+    (7,1,0,0), # N-aro
+    (7,0,1,1), # N-hdon-hacc
+    (7,1,0,1), # N-aro-hacc
+    (7,1,1,0), # N-aro-hdon
+    (8,0,0,0), # O
+    (8,0,0,1), # O-hacc
+    (8,0,1,1), # O-hdon-hacc
+    (16,0,0,0), #S
+]
+
+REC_DESC_H = [
+    (1,0,0,0), # H
+    (6,0,0,0), # C
+    (6,1,0,0), # C-hacc
+    (7,0,0,0), # N
+    (7,0,0,1), # N-aro
+    (7,0,1,0), # N-hdon
+    (7,1,0,0), # N-hacc
+    (7,0,1,1), # N-hdon-aro
+    (7,1,0,1), # N-hacc-aro
+    (7,1,1,0), # N-hacc-hdon
+    (8,0,0,0), # O
+    (8,0,0,1), # O-aro
+    (8,0,1,1), # O-hdon-aro
+    (16,0,0,0), #S
+]
+    
+def rec_typer_desc(t):
+    '''descriptive types'''
+    num, hacc, hdon, aro, _ = t
+    
+    f = (num,hacc,hdon,aro)
+    
+    if f in REC_DESC:
+        return REC_DESC.index(f)
+    else:
+        return -1
+    
+def rec_typer_desc_h(t):
+    '''descriptive types'''
+    num, hacc, hdon, aro, _ = t
+    
+    f = (num,hacc,hdon,aro)
+    
+    if f in REC_DESC_H:
+        return REC_DESC_H.index(f)
+    else:
+        return -1
+    
+def lig_typer_single(t):
+    if t != 1:
+        return 0
+    else:
+        return -1
+
+def lig_typer_single_h(t):
+    return 0
+
+def lig_typer_simple(t):
+    BASIC_TYPES = [6,7,8]
+    
+    if t in BASIC_TYPES:
+        return BASIC_TYPES.index(t)
+    else:
+        return -1
+    
+def lig_typer_simple_h(t):
+    BASIC_TYPES = [1,6,7,8]
     
-    def f(x):
-        if x in atom_mapping:
-            return atom_mapping[x]
-        else:
-            return -1
+    if t in BASIC_TYPES:
+        return BASIC_TYPES.index(t)
+    else:
+        return -1
     
-    return f
+def lig_typer_desc(t):
+    DESC_TYPES = [6,7,8,16,9,15,17,35,5,53]
+    
+    if t in DESC_TYPES:
+        return DESC_TYPES.index(t)
+    else:
+        return -1
+    
+def lig_typer_desc_h(t):
+    DESC_TYPES = [1,6,7,8,16,9,15,17,35,5,53]
+    
+    if t in DESC_TYPES:
+        return DESC_TYPES.index(t)
+    else:
+        return -1
+
+
+REC_TYPER = {
+    'single': rec_typer_single,
+    'single_h': rec_typer_single_h,
+    'simple': rec_typer_basic,
+    'simple_h': rec_typer_basic_h,
+    'desc': rec_typer_desc,
+    'desc_h': rec_typer_desc_h
+}
+
+LIG_TYPER = {
+    'single': lig_typer_single,
+    'single_h': lig_typer_single_h,
+    'simple': lig_typer_simple,
+    'simple_h': lig_typer_simple_h,
+    'desc': lig_typer_desc,
+    'desc_h': lig_typer_desc_h
+}
 
 
 class FragmentDataset(Dataset):
@@ -37,15 +170,17 @@ class FragmentDataset(Dataset):
     Utility class to work with the packed fragments.h5 format
     '''
     
-    def __init__(self, fragment_file, fingerprint_file, filter_rec=None, atom_types=DEFAULT_TYPES, fdist_min=None, fdist_max=None, fmass_min=None, fmass_max=None):
+    def __init__(self, fragment_file, fingerprint_file, rec_typer, lig_typer, filter_rec=None, 
+        fdist_min=None, fdist_max=None, fmass_min=None, fmass_max=None, verbose=False):
         '''
         Initialize the fragment dataset
         
         Params:
         - fragment_file: path to fragments.h5
         - fingerprint_file: path to fingerprints.h5
+        - rec_typer: function to map receptor rows to layer index
+        - lig_typer: function to map ligand rows to layer index
         - filter_rec: list of receptor ids to use (or None to use all)
-        - atom_types: which atom types to use as layers
 
         Filtering options:
         - fdist_min: minimum fragment distance
@@ -53,9 +188,11 @@ class FragmentDataset(Dataset):
         - fmass_min: minimum fragment mass (Da)
         - fmass_max: maximum fragment mass (Da)
         '''
+        self.verbose = verbose
+
         #  load receptor/fragment information
-        self.rec = self.load_rec(fragment_file, atom_types)
-        self.frag = self.load_fragments(fragment_file, atom_types)
+        self.rec = self.load_rec(fragment_file, rec_typer)
+        self.frag = self.load_fragments(fragment_file, lig_typer)
 
         # load fingerprint information
         self.fingerprints = self.load_fingerprints(fingerprint_file)
@@ -91,19 +228,22 @@ class FragmentDataset(Dataset):
 
         self.valid_fingerprints = self.compute_valid_fingerprints()
 
-    def load_rec(self, fragment_file, atom_types):
+    def load_rec(self, fragment_file, rec_typer):
         '''Load receptor information'''
         f = h5py.File(fragment_file, 'r')
         
-        rec_data = f['rec_data'][()]
+        rec_coords = f['rec_coords'][()]
+        rec_types = f['rec_types'][()]
         rec_lookup = f['rec_lookup'][()]
         
-        # unpack rec data into separate structures
-        rec_coords = rec_data[:,:3].astype(np.float32)
-        rec_types = rec_data[:,3].reshape(-1,1).astype(np.int32)
-        
-        rec_remapped = np.vectorize(remap_atoms(atom_types))(rec_types)
-        
+        r = range(len(rec_types))
+        if self.verbose:
+            r = tqdm.tqdm(r, desc='Remap receptor atoms')
+
+        rec_remapped = np.zeros(len(rec_types)).astype(np.int32)
+        for i in r:
+            rec_remapped[i] = rec_typer(rec_types[i])
+
         # create rec mapping
         rec_mapping = {}
         for i in range(len(rec_lookup)):
@@ -121,7 +261,7 @@ class FragmentDataset(Dataset):
         
         return rec
         
-    def load_fragments(self, fragment_file, atom_types):
+    def load_fragments(self, fragment_file, lig_typer):
         '''Load fragment information'''
 
         f = h5py.File(fragment_file, 'r')
@@ -134,13 +274,17 @@ class FragmentDataset(Dataset):
         
         # unpack frag data into separate structures
         frag_coords = frag_data[:,:3].astype(np.float32)
-        frag_types = frag_data[:,3].reshape(-1,1).astype(np.int32)
+        frag_types = frag_data[:,3].astype(np.int32)
         
-        frag_remapped = np.vectorize(remap_atoms(atom_types))(frag_types)
+        frag_remapped = np.vectorize(lig_typer)(frag_types)
         
         # find and save connection point
+        r = range(len(frag_lookup))
+        if self.verbose:
+            r = tqdm.tqdm(r, desc='Frag connection point')
+
         frag_conn = np.zeros((len(frag_lookup), 3))
-        for i in range(len(frag_lookup)):
+        for i in r:
             _,f_start,f_end,_,_ = frag_lookup[i]
             fdat = frag_data[f_start:f_end]
             

leadopt/grid_util.py

@@ -67,7 +67,8 @@ def gpu_gridify(grid, width, res, center, rot, atom_num, atom_coords, atom_types
     while i < atom_num:
         # fetch atom
         fx, fy, fz = atom_coords[i]
-        ft = atom_types[i][0]
+        # ft = atom_types[i][0]
+        ft = atom_types[i]
         i += 1
         
         # invisible atoms
@@ -152,13 +153,15 @@ def mol_gridify(
     )
     
 
-def get_batch(data, batch_set=None, batch_size=16, width=48, res=0.5, ignore_receptor=False, ignore_parent=False, include_freq=False):
+def get_batch(data, rec_channels, parent_channels, batch_set=None, batch_size=16, width=48, res=0.5, ignore_receptor=False, ignore_parent=False, include_freq=False):
     
     assert (not (ignore_receptor and ignore_parent)), "Can't ignore parent and receptor!"
 
-    dim = 18
-    if ignore_receptor or ignore_parent:
-        dim = 9
+    dim = 0
+    if not ignore_receptor:
+        dim += rec_channels
+    if not ignore_parent:
+        dim += parent_channels
 
     # create a tensor with shared memory on the gpu
     t, grid = make_tensor((batch_size, dim, width, width, width))
@@ -182,7 +185,7 @@ def get_batch(data, batch_set=None, batch_size=16, width=48, res=0.5, ignore_rec
             mol_gridify(grid, r_coords, r_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=0)
         else:
             mol_gridify(grid, p_coords, p_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=0)
-            mol_gridify(grid, r_coords, r_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=9)
+            mol_gridify(grid, r_coords, r_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=parent_channels)
         
         fingerprints[i] = fp
         freq[i] = extra['freq']
@@ -196,63 +199,63 @@ def get_batch(data, batch_set=None, batch_size=16, width=48, res=0.5, ignore_rec
         return t, t_fingerprints, batch_set
 
 
-def get_batch_dual(data, batch_set=None, batch_size=16, width=48, res=0.5, ignore_receptor=False, ignore_parent=False):
+# def get_batch_dual(data, batch_set=None, batch_size=16, width=48, res=0.5, ignore_receptor=False, ignore_parent=False):
 
-    # get batch
-    t, fp, batch_set = get_batch(data, batch_set, batch_size, width, res, ignore_receptor, ignore_parent)
+#     # get batch
+#     t, fp, batch_set = get_batch(data, batch_set, batch_size, width, res, ignore_receptor, ignore_parent)
 
-    f = data.fingerprints['fingerprint_data']
+#     f = data.fingerprints['fingerprint_data']
 
-    # corrupt fingerprints
-    false_fp = torch.clone(fp)
-    for i in range(batch_size):
-        # idx = np.random.randint(fp.shape[1])
-        # false_fp[i,idx] = (1 - false_fp[i,idx]) # flip
-        idx = np.random.randint(f.shape[0])
-        false_fp[i] = torch.Tensor(f[idx]) # replace
+#     # corrupt fingerprints
+#     false_fp = torch.clone(fp)
+#     for i in range(batch_size):
+#         # idx = np.random.randint(fp.shape[1])
+#         # false_fp[i,idx] = (1 - false_fp[i,idx]) # flip
+#         idx = np.random.randint(f.shape[0])
+#         false_fp[i] = torch.Tensor(f[idx]) # replace
 
-    comb_t = torch.cat([t,t], axis=0)
-    comb_fp = torch.cat([fp, false_fp], axis=0)
+#     comb_t = torch.cat([t,t], axis=0)
+#     comb_fp = torch.cat([fp, false_fp], axis=0)
 
-    y = torch.zeros((batch_size * 2,1)).cuda()
-    y[:batch_size] = 1
+#     y = torch.zeros((batch_size * 2,1)).cuda()
+#     y[:batch_size] = 1
 
-    return (comb_t, comb_fp, y, batch_set)
+#     return (comb_t, comb_fp, y, batch_set)
 
 
-def get_batch_full(data, batch_set=None, batch_size=16, width=48, res=0.5, ignore_receptor=False, ignore_parent=False):
+# def get_batch_full(data, batch_set=None, batch_size=16, width=48, res=0.5, ignore_receptor=False, ignore_parent=False):
     
-    assert (not (ignore_receptor and ignore_parent)), "Can't ignore parent and receptor!"
+#     assert (not (ignore_receptor and ignore_parent)), "Can't ignore parent and receptor!"
 
-    dim = 18
-    if ignore_receptor or ignore_parent:
-        dim = 9
+#     dim = 18
+#     if ignore_receptor or ignore_parent:
+#         dim = 9
 
-    # create a tensor with shared memory on the gpu
-    t_context, grid_context = make_tensor((batch_size, dim, width, width, width))
-    t_frag, grid_frag = make_tensor((batch_size, 9, width, width, width))
+#     # create a tensor with shared memory on the gpu
+#     t_context, grid_context = make_tensor((batch_size, dim, width, width, width))
+#     t_frag, grid_frag = make_tensor((batch_size, 9, width, width, width))
     
-    if batch_set is None:
-        batch_set = np.random.choice(len(data), size=batch_size, replace=False)
+#     if batch_set is None:
+#         batch_set = np.random.choice(len(data), size=batch_size, replace=False)
     
-    for i in range(len(batch_set)):
-        idx = batch_set[i]
-        f_coords, f_types, p_coords, p_types, r_coords, r_types, conn, fp = data[idx]
+#     for i in range(len(batch_set)):
+#         idx = batch_set[i]
+#         f_coords, f_types, p_coords, p_types, r_coords, r_types, conn, fp = data[idx]
         
-        # random rotation
-        rot = rand_rot()
+#         # random rotation
+#         rot = rand_rot()
         
-        if ignore_receptor:
-            mol_gridify(grid_context, p_coords, p_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=0)
-        elif ignore_parent:
-            mol_gridify(grid_context, r_coords, r_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=0)
-        else:
-            mol_gridify(grid_context, p_coords, p_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=0)
-            mol_gridify(grid_context, r_coords, r_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=9)
+#         if ignore_receptor:
+#             mol_gridify(grid_context, p_coords, p_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=0)
+#         elif ignore_parent:
+#             mol_gridify(grid_context, r_coords, r_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=0)
+#         else:
+#             mol_gridify(grid_context, p_coords, p_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=0)
+#             mol_gridify(grid_context, r_coords, r_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=9)
         
-        mol_gridify(grid_frag, f_coords, f_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=0)
+#         mol_gridify(grid_frag, f_coords, f_types, batch_i=i, center=conn, width=width, res=res, rot=rot, layer_offset=0)
 
-    return t_context, t_frag, batch_set
+#     return t_context, t_frag, batch_set
 
 
 def get_raw_batch(r_coords, r_types, p_coords, p_types, conn, num_samples=32, width=24, res=1, r_dim=9, p_dim=9):

leadopt/infer.py

@@ -12,7 +12,7 @@ import h5py
 import tqdm
 
 from leadopt.grid_util import get_raw_batch
-from leadopt.util import generate_fragments
+import