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import numpy as np
import random
class ContigMap:
"""
Class for doing mapping.
Inherited from Inpainting. To update at some point.
Supports multichain or multiple crops from a single receptor chain.
Also supports indexing jump (+200) or not, based on contig input.
Default chain outputs are inpainted chains as A (and B, C etc if multiple chains), and all fragments of receptor chain on the next one (generally B)
Output chains can be specified. Sequence must be the same number of elements as in contig string
"""
def __init__(
self,
parsed_pdb,
contigs=None,
inpaint_seq=None,
inpaint_str=None,
length=None,
ref_idx=None,
hal_idx=None,
idx_rf=None,
inpaint_seq_tensor=None,
inpaint_str_tensor=None,
topo=False,
provide_seq=None,
):
# sanity checks
if contigs is None and ref_idx is None:
sys.exit("Must either specify a contig string or precise mapping")
if idx_rf is not None or hal_idx is not None or ref_idx is not None:
if idx_rf is None or hal_idx is None or ref_idx is None:
sys.exit(
"If you're specifying specific contig mappings, the reference and output positions must be specified, AND the indexing for RoseTTAFold (idx_rf)"
)
self.chain_order = "ABCDEFGHIJKLMNOPQRSTUVWXYZ"
if length is not None:
if "-" not in length:
self.length = [int(length), int(length) + 1]
else:
self.length = [int(length.split("-")[0]), int(length.split("-")[1]) + 1]
else:
self.length = None
self.ref_idx = ref_idx
self.hal_idx = hal_idx
self.idx_rf = idx_rf
self.inpaint_seq = (
"/".join(inpaint_seq).split("/") if inpaint_seq is not None else None
)
self.inpaint_str = (
"/".join(inpaint_str).split("/") if inpaint_str is not None else None
)
self.inpaint_seq_tensor = inpaint_seq_tensor
self.inpaint_str_tensor = inpaint_str_tensor
self.parsed_pdb = parsed_pdb
self.topo = topo
if ref_idx is None:
# using default contig generation, which outputs in rosetta-like format
self.contigs = contigs
(
self.sampled_mask,
self.contig_length,
self.n_inpaint_chains,
) = self.get_sampled_mask()
self.receptor_chain = self.chain_order[self.n_inpaint_chains]
(
self.receptor,
self.receptor_hal,
self.receptor_rf,
self.inpaint,
self.inpaint_hal,
self.inpaint_rf,
) = self.expand_sampled_mask()
self.ref = self.inpaint + self.receptor
self.hal = self.inpaint_hal + self.receptor_hal
self.rf = self.inpaint_rf + self.receptor_rf
else:
# specifying precise mappings
self.ref = ref_idx
self.hal = hal_idx
self.rf = idx_rf
self.mask_1d = [False if i == ("_", "_") else True for i in self.ref]
# take care of sequence and structure masking
if self.inpaint_seq_tensor is None:
if self.inpaint_seq is not None:
self.inpaint_seq = self.get_inpaint_seq_str(self.inpaint_seq)
else:
self.inpaint_seq = np.array(
[True if i != ("_", "_") else False for i in self.ref]
)
else:
self.inpaint_seq = self.inpaint_seq_tensor
if self.inpaint_str_tensor is None:
if self.inpaint_str is not None:
self.inpaint_str = self.get_inpaint_seq_str(self.inpaint_str)
else:
self.inpaint_str = np.array(
[True if i != ("_", "_") else False for i in self.ref]
)
else:
self.inpaint_str = self.inpaint_str_tensor
# get 0-indexed input/output (for trb file)
(
self.ref_idx0,
self.hal_idx0,
self.ref_idx0_inpaint,
self.hal_idx0_inpaint,
self.ref_idx0_receptor,
self.hal_idx0_receptor,
) = self.get_idx0()
self.con_ref_pdb_idx = [i for i in self.ref if i != ("_", "_")]
# Handle provide seq. This is zero-indexed, and used only for partial diffusion
if provide_seq is not None:
for i in provide_seq:
if "-" in i:
self.inpaint_seq[
int(i.split("-")[0]) : int(i.split("-")[1]) + 1
] = True
else:
self.inpaint_seq[int(i)] = True
def get_sampled_mask(self):
"""
Function to get a sampled mask from a contig.
"""
length_compatible = False
count = 0
while length_compatible is False:
inpaint_chains = 0
contig_list = self.contigs[0].strip().split()
sampled_mask = []
sampled_mask_length = 0
# allow receptor chain to be last in contig string
if all([i[0].isalpha() for i in contig_list[-1].split("/")]):
contig_list[-1] = f"{contig_list[-1]}/0"
for con in contig_list:
if (
all([i[0].isalpha() for i in con.split("/")[:-1]])
and con.split("/")[-1] == "0"
) or self.topo is True:
# receptor chain
sampled_mask.append(con)
else:
inpaint_chains += 1
# chain to be inpainted. These are the only chains that count towards the length of the contig
subcons = con.split("/")
subcon_out = []
for subcon in subcons:
if subcon[0].isalpha():
subcon_out.append(subcon)
if "-" in subcon:
sampled_mask_length += (
int(subcon.split("-")[1])
- int(subcon.split("-")[0][1:])
+ 1
)
else:
sampled_mask_length += 1
else:
if "-" in subcon:
length_inpaint = random.randint(
int(subcon.split("-")[0]), int(subcon.split("-")[1])
)
subcon_out.append(f"{length_inpaint}-{length_inpaint}")
sampled_mask_length += length_inpaint
elif subcon == "0":
subcon_out.append("0")
else:
length_inpaint = int(subcon)
subcon_out.append(f"{length_inpaint}-{length_inpaint}")
sampled_mask_length += int(subcon)
sampled_mask.append("/".join(subcon_out))
# check length is compatible
if self.length is not None:
if (
sampled_mask_length >= self.length[0]
and sampled_mask_length < self.length[1]
):
length_compatible = True
else:
length_compatible = True
count += 1
if count == 100000: # contig string incompatible with this length
sys.exit("Contig string incompatible with --length range")
return sampled_mask, sampled_mask_length, inpaint_chains
def expand_sampled_mask(self):
chain_order = "ABCDEFGHIJKLMNOPQRSTUVWXYZ"
receptor = []
inpaint = []
receptor_hal = []
inpaint_hal = []
receptor_idx = 1
inpaint_idx = 1
inpaint_chain_idx = -1
receptor_chain_break = []
inpaint_chain_break = []
for con in self.sampled_mask:
if (
all([i[0].isalpha() for i in con.split("/")[:-1]])
and con.split("/")[-1] == "0"
) or self.topo is True:
# receptor chain
subcons = con.split("/")[:-1]
assert all(
[i[0] == subcons[0][0] for i in subcons]
), "If specifying fragmented receptor in a single block of the contig string, they MUST derive from the same chain"
assert all(
int(subcons[i].split("-")[0][1:])
< int(subcons[i + 1].split("-")[0][1:])
for i in range(len(subcons) - 1)
), "If specifying multiple fragments from the same chain, pdb indices must be in ascending order!"
for idx, subcon in enumerate(subcons):
ref_to_add = [
(subcon[0], i)
for i in np.arange(
int(subcon.split("-")[0][1:]), int(subcon.split("-")[1]) + 1
)
]
receptor.extend(ref_to_add)
receptor_hal.extend(
[
(self.receptor_chain, i)
for i in np.arange(
receptor_idx, receptor_idx + len(ref_to_add)
)
]
)
receptor_idx += len(ref_to_add)
if idx != len(subcons) - 1:
idx_jump = (
int(subcons[idx + 1].split("-")[0][1:])
- int(subcon.split("-")[1])
- 1
)
receptor_chain_break.append(
(receptor_idx - 1, idx_jump)
) # actual chain break in pdb chain
else:
receptor_chain_break.append(
(receptor_idx - 1, 200)
) # 200 aa chain break
else:
inpaint_chain_idx += 1
for subcon in con.split("/"):
if subcon[0].isalpha():
ref_to_add = [
(subcon[0], i)
for i in np.arange(
int(subcon.split("-")[0][1:]),
int(subcon.split("-")[1]) + 1,
)
]
inpaint.extend(ref_to_add)
inpaint_hal.extend(
[
(chain_order[inpaint_chain_idx], i)
for i in np.arange(
inpaint_idx, inpaint_idx + len(ref_to_add)
)
]
)
inpaint_idx += len(ref_to_add)
else:
inpaint.extend([("_", "_")] * int(subcon.split("-")[0]))
inpaint_hal.extend(
[
(chain_order[inpaint_chain_idx], i)
for i in np.arange(
inpaint_idx, inpaint_idx + int(subcon.split("-")[0])
)
]
)
inpaint_idx += int(subcon.split("-")[0])
inpaint_chain_break.append((inpaint_idx - 1, 200))
if self.topo is True or inpaint_hal == []:
receptor_hal = [(i[0], i[1]) for i in receptor_hal]
else:
receptor_hal = [
(i[0], i[1] + inpaint_hal[-1][1]) for i in receptor_hal
] # rosetta-like numbering
# get rf indexes, with chain breaks
inpaint_rf = np.arange(0, len(inpaint))
receptor_rf = np.arange(len(inpaint) + 200, len(inpaint) + len(receptor) + 200)
for ch_break in inpaint_chain_break[:-1]:
receptor_rf[:] += 200
inpaint_rf[ch_break[0] :] += ch_break[1]
for ch_break in receptor_chain_break[:-1]:
receptor_rf[ch_break[0] :] += ch_break[1]
return (
receptor,
receptor_hal,
receptor_rf.tolist(),
inpaint,
inpaint_hal,
inpaint_rf.tolist(),
)
def get_inpaint_seq_str(self, inpaint_s):
"""
function to generate inpaint_str or inpaint_seq masks specific to this contig
"""
s_mask = np.copy(self.mask_1d)
inpaint_s_list = []
for i in inpaint_s:
if "-" in i:
inpaint_s_list.extend(
[
(i[0], p)
for p in range(
int(i.split("-")[0][1:]), int(i.split("-")[1]) + 1
)
]
)
else:
inpaint_s_list.append((i[0], int(i[1:])))
for res in inpaint_s_list:
if res in self.ref:
s_mask[self.ref.index(res)] = False # mask this residue
return np.array(s_mask)
def get_idx0(self):
ref_idx0 = []
hal_idx0 = []
ref_idx0_inpaint = []
hal_idx0_inpaint = []
ref_idx0_receptor = []
hal_idx0_receptor = []
for idx, val in enumerate(self.ref):
if val != ("_", "_"):
assert val in self.parsed_pdb["pdb_idx"], f"{val} is not in pdb file!"
hal_idx0.append(idx)
ref_idx0.append(self.parsed_pdb["pdb_idx"].index(val))
for idx, val in enumerate(self.inpaint):
if val != ("_", "_"):
hal_idx0_inpaint.append(idx)
ref_idx0_inpaint.append(self.parsed_pdb["pdb_idx"].index(val))
for idx, val in enumerate(self.receptor):
if val != ("_", "_"):
hal_idx0_receptor.append(idx)
ref_idx0_receptor.append(self.parsed_pdb["pdb_idx"].index(val))
return (
ref_idx0,
hal_idx0,
ref_idx0_inpaint,
hal_idx0_inpaint,
ref_idx0_receptor,
hal_idx0_receptor,
)
def get_mappings(self):
mappings = {}
mappings["con_ref_pdb_idx"] = [i for i in self.inpaint if i != ("_", "_")]
mappings["con_hal_pdb_idx"] = [
self.inpaint_hal[i]
for i in range(len(self.inpaint_hal))
if self.inpaint[i] != ("_", "_")
]
mappings["con_ref_idx0"] = np.array(self.ref_idx0_inpaint)
mappings["con_hal_idx0"] = np.array(self.hal_idx0_inpaint)
if self.inpaint != self.ref:
mappings["complex_con_ref_pdb_idx"] = [
i for i in self.ref if i != ("_", "_")
]
mappings["complex_con_hal_pdb_idx"] = [
self.hal[i] for i in range(len(self.hal)) if self.ref[i] != ("_", "_")
]
mappings["receptor_con_ref_pdb_idx"] = [
i for i in self.receptor if i != ("_", "_")
]
mappings["receptor_con_hal_pdb_idx"] = [
self.receptor_hal[i]
for i in range(len(self.receptor_hal))
if self.receptor[i] != ("_", "_")
]
mappings["complex_con_ref_idx0"] = np.array(self.ref_idx0)
mappings["complex_con_hal_idx0"] = np.array(self.hal_idx0)
mappings["receptor_con_ref_idx0"] = np.array(self.ref_idx0_receptor)
mappings["receptor_con_hal_idx0"] = np.array(self.hal_idx0_receptor)
mappings["inpaint_str"] = self.inpaint_str
mappings["inpaint_seq"] = self.inpaint_seq
mappings["sampled_mask"] = self.sampled_mask
mappings["mask_1d"] = self.mask_1d
return mappings
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