Source code for EquiDock: Independent SE(3)-Equivariant Models for End-to-End Rigid Protein Docking (ICLR 2022)
Please cite "Independent SE(3)-Equivariant Models for End-to-End Rigid Protein Docking", Ganea et. al, Spotlight @ ICLR 2022
Dependencies
python==3.9.10
numpy==1.22.1
cuda==10.1
torch==1.10.2
dgl==0.7.0
biopandas==0.2.8
ot==0.7.0
rdkit==2021.09.4
dgllife==0.2.8
joblib==1.1.0
DB5.5 data
The raw DB5.5 dataset was already placed in the data directory from the original source:
https://zlab.umassmed.edu/benchmark/ or https://github.com/drorlab/DIPS
The raw pdb files of DB5.5 dataset are in the directory ./data/benchmark5.5/structures
Then preprocess the raw data as follows to prepare data for rigid body docking:
# prepare data for rigid body docking
python preprocess_raw_data.py -n_jobs 40 -data db5 -graph_nodes residues -graph_cutoff 30 -graph_max_neighbor 10 -graph_residue_loc_is_alphaC -pocket_cutoff 8
By default, preprocess_raw_data.py uses 10 neighbor for each node when constructing the graph and uses only residues (coordinates being those of the alpha carbons). After running preprocess_raw_data.py you will get following ready-for-training data directory:
./cache/db5_residues_maxneighbor_10_cutoff_30.0_pocketCut_8.0/cv_0/
with files
$ ls cache/db5_residues_maxneighbor_10_cutoff_30.0_pocketCut_8.0/cv_0/
label_test.pkl label_val.pkl ligand_graph_train.bin receptor_graph_test.bin receptor_graph_val.bin
label_train.pkl ligand_graph_test.bin ligand_graph_val.bin receptor_graph_train.bin
DIPS data
Download the dataset (see https://github.com/drorlab/DIPS and https://github.com/amorehead/DIPS-Plus) :
mkdir -p ./DIPS/raw/pdb
rsync -rlpt -v -z --delete --port=33444 \
rsync.rcsb.org::ftp_data/biounit/coordinates/divided/ ./DIPS/raw/pdb
Follow the following first steps from https://github.com/amorehead/DIPS-Plus :
# Create data directories (if not already created):
mkdir project/datasets/DIPS/raw project/datasets/DIPS/raw/pdb project/datasets/DIPS/interim project/datasets/DIPS/interim/external_feats project/datasets/DIPS/final project/datasets/DIPS/final/raw project/datasets/DIPS/final/processed
# Download the raw PDB files:
rsync -rlpt -v -z --delete --port=33444 --include='*.gz' --include='*.xz' --include='*/' --exclude '*' \
rsync.rcsb.org::ftp_data/biounit/coordinates/divided/ project/datasets/DIPS/raw/pdb
# Extract the raw PDB files:
python3 project/datasets/builder/extract_raw_pdb_gz_archives.py project/datasets/DIPS/raw/pdb
# Process the raw PDB data into associated pair files:
python3 project/datasets/builder/make_dataset.py project/datasets/DIPS/raw/pdb project/datasets/DIPS/interim --num_cpus 28 --source_type rcsb --bound
# Apply additional filtering criteria:
python3 project/datasets/builder/prune_pairs.py project/datasets/DIPS/interim/pairs project/datasets/DIPS/filters project/datasets/DIPS/interim/pairs-pruned --num_cpus 28
Then, place file utils/partition_dips.py in the DIPS/src/ folder, use the pairs-postprocessed-*.txt files for the actual data splits used in our paper, and run from the DIPS/ folder the command: python src/partition_dips.py data/DIPS/interim/pairs-pruned/. This creates the corresponding train/test/validation splits (again, using the exact splits in pairs-postprocessed-*.txt) of the 42K filtered pairs in DIPS. You should now have the following directory:
$ ls ./DIPS/data/DIPS/interim/pairs-pruned
0g a6 ax bo cf d6 dx eo ff g6 gx ho if j6 jx ko lf m6 mx no of p6 pt qk rb s2 st tk ub v2 vt wk xb y2 yt zk
17 a7 ay bp cg d7 dy ep fg g7 gy hp ig j7 jy kp lg m7 my np og p7 pu ql rc s3 su tl uc v3 vu wl xc y3 yu zl
1a a8 az bq ch d8 dz eq fh g8 gz hq ih j8 jz kq lh m8 mz nq oh p8 pv qm rd s4 sv tm ud v4 vv wm xd y4 yv zm
1b a9 b0 br ci d9 e0 er fi g9 h0 hr ii j9 k0 kr li m9 n0 nr oi p9 pw qn re s5 sw tn ue v5 vw wn xe y5 yw zn
1g aa b1 bs cj da e1 es fj ga h1 hs ij ja k1 ks lj ma n1 ns oj pa px qo rf s6 sx to uf v6 vx wo xf y6 yx zo
2a ab b2 bt ck db e2 et fk gb h2 ht ik jb k2 kt lk mb n2 nt ok pairs-postprocessed-test.txt py qp rg s7 sy tp ug v7 vy wp xg y7 yy zp
2c ac b3 bu cl dc e3 eu fl gc h3 hu il jc k3 ku ll mc n3 nu ol pairs-postprocessed-train.txt pz qq rh s8 sz tq uh v8 vz wq xh y8 yz zq
2e ad b4 bv cm dd e4 ev fm gd h4 hv im jd k4 kv lm md n4 nv om pairs-postprocessed.txt q0 qr ri s9 t0 tr ui v9 w0 wr xi y9 z0 zr
2g ae b5 bw cn de e5 ew fn ge h5 hw in je k5 kw ln me n5 nw on pairs-postprocessed-val.txt q1 qs rj sa t1 ts uj va w1 ws xj ya z1 zs
3c af b6 bx co df e6 ex fo gf h6 hx io jf k6 kx lo mf n6 nx oo pb q2 qt rk sb t2 tt uk vb w2 wt xk yb z2 zt
3g ag b7 by cp dg e7 ey fp gg h7 hy ip jg k7 ky lp mg n7 ny op pc q3 qu rl sc t3 tu ul vc w3 wu xl yc z3 zu
48 ah b8 bz cq dh e8 ez fq gh h8 hz iq jh k8 kz lq mh n8 nz oq pd q4 qv rm sd t4 tv um vd w4 wv xm yd z4 zv
4g ai b9 c0 cr di e9 f0 fr gi h9 i0 ir ji k9 l0 lr mi n9 o0 or pe q5 qw rn se t5 tw un ve w5 ww xn ye z5 zw
56 aj ba c1 cs dj ea f1 fs gj ha i1 is jj ka l1 ls mj na o1 os pf q6 qx ro sf t6 tx uo vf w6 wx xo yf z6 zx
5c ak bb c2 ct dk eb f2 ft gk hb i2 it jk kb l2 lt mk nb o2 ot pg q7 qy rp sg t7 ty up vg w7 wy xp yg z7 zy
6g al bc c3 cu dl ec f3 fu gl hc i3 iu jl kc l3 lu ml nc o3 ou ph q8 qz rq sh t8 tz uq vh w8 wz xq yh z8 zz
7g am bd c4 cv dm ed f4 fv gm hd i4 iv jm kd l4 lv mm nd o4 ov pi q9 r0 rr si t9 u0 ur vi w9 x0 xr yi z9
87 an be c5 cw dn ee f5 fw gn he i5 iw jn ke l5 lw mn ne o5 ow pj qa r1 rs sj ta u1 us vj wa x1 xs yj za
8g ao bf c6 cx do ef f6 fx go hf i6 ix jo kf l6 lx mo nf o6 ox pk qb r2 rt sk tb u2 ut vk wb x2 xt yk zb
9g ap bg c7 cy dp eg f7 fy gp hg i7 iy jp kg l7 ly mp ng o7 oy pl qc r3 ru sl tc u3 uu vl wc x3 xu yl zc
9h aq bh c8 cz dq eh f8 fz gq hh i8 iz jq kh l8 lz mq nh o8 oz pm qd r4 rv sm td u4 uv vm wd x4 xv ym zd
a0 ar bi c9 d0 dr ei f9 g0 gr hi i9 j0 jr ki l9 m0 mr ni o9 p0 pn qe r5 rw sn te u5 uw vn we x5 xw yn ze
a1 as bj ca d1 ds ej fa g1 gs hj ia j1 js kj la m1 ms nj oa p1 po qf r6 rx so tf u6 ux vo wf x6 xx yo zf
a2 at bk cb d2 dt ek fb g2 gt hk ib j2 jt kk lb m2 mt nk ob p2 pp qg r7 ry sp tg u7 uy vp wg x7 xy yp zg
a3 au bl cc d3 du el fc g3 gu hl ic j3 ju kl lc m3 mu nl oc p3 pq qh r8 rz sq th u8 uz vq wh x8 xz yq zh
a4 av bm cd d4 dv em fd g4 gv hm id j4 jv km ld m4 mv nm od p4 pr qi r9 s0 sr ti u9 v0 vr wi x9 y0 yr zi
a5 aw bn ce d5 dw en fe g5 gw hn ie j5 jw kn le m5 mw nn oe p5 ps qj ra s1 ss tj ua v1 vs wj xa y1 ys zj
Then preprocess the raw data as follow to prepare data for rigid body docking:
# prepare data for rigid body docking
python preprocess_raw_data.py -n_jobs 60 -data dips -graph_nodes residues -graph_cutoff 30 -graph_max_neighbor 10 -graph_residue_loc_is_alphaC -pocket_cutoff 8 -data_fraction 1.0
You should now obtain the following cache data directory:
$ ls cache/dips_residues_maxneighbor_10_cutoff_30.0_pocketCut_8.0/cv_0/
label_test.pkl ligand_graph_val.bin receptor_graph_frac_1.0_train.bin
label_val.pkl ligand_graph_frac_1.0_train.bin receptor_graph_test.bin
label_frac_1.0_train.pkl ligand_graph_test.bin receptor_graph_val.bin
Training
On GPU (works also on CPU, but it's very slow):
CUDA_VISIBLE_DEVICES=0 python -m src.train -hyper_search
or just specify your own params if you don't want to do hyperparam search. This will create checkpoints, tensorboard logs (you can visualize with tensorboard) and will store all stdout/stderr in a log file. This will train a model on DIPS first and, then, fine-tune it on DB5. Use -toy to train on DB5 only.
Data splits
In our paper, we used the train/validation/test splits given by the files
DIPS: DIPS/data/DIPS/interim/pairs-pruned/pairs-postprocessed-*.txt
DB5: data/benchmark5.5/cv/cv_0/*.txt
Inference
See inference_rigid.py.
Pretrained models
Our paper pretrained models are available in folder checkpts/. By loading those (as in inference_rigid.py), you can also see which hyperparameters were used in those models (or directly from their names).
Test and reproduce paper's numbers
Test sets used in our paper are given in test_sets_pdb/. Ground truth (bound) structures are in test_sets_pdb/dips_test_random_transformed/complexes/, while unbound structures (i.e., randomly rotated and translated ligands and receptors) are in test_sets_pdb/dips_test_random_transformed/random_transformed/ and you should precisely use those for your predictions (or at least the ligands, while using the ground truth receptors like we do in inference_rigid.py). This test set was originally generated as a randomly sampled family-based subset of complexes in ./DIPS/data/DIPS/interim/pairs-pruned/pairs-postprocessed-test.txt using the file src/test_all_methods/testset_random_transf.py.
Run python -m src.inference_rigid to produce EquiDock's outputs for all test files. This will create a new directory of PDB output files in test_sets_pdb/.
Get RMSD numbers from our papers using python -m src.test_all_methods.eval_pdb_outputset. You can use this script to evaluate all other baselines. Baselines' output PDB files are also provided in test_sets_pdb/
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