Read ProteinMPNN paper.
To run ProteinMPNN clone this github repo and install Python>=3.0, PyTorch, Numpy.
Full protein backbone models: vanilla_model_weights/v_48_002.pt, v_48_010.pt, v_48_020.pt, v_48_030.pt.
CA only models: ca_model_weights/v_48_002.pt, v_48_010.pt, v_48_020.pt. Enable flag --ca_only to use these models.
Helper scripts: helper_scripts - helper functions to parse PDBs, assign which chains to design, which residues to fix, adding AA bias, tying residues etc.
Code organization:
protein_mpnn_run.py- the main script to initialialize and run the model.protein_mpnn_utils.py- utility functions for the main script.examples/- simple code examples.inputs/- input PDB files for examplesoutputs/- outputs from examplescolab_notebooks/- Google Colab examples
Input flags for protein_mpnn_run.py:
argparser.add_argument("--ca_only", action="store_true", default=False, help="Parse CA-only structures and use CA-only models (default: false)")
argparser.add_argument("--path_to_model_weights", type=str, default="", help="Path to model weights folder;")
argparser.add_argument("--model_name", type=str, default="v_48_020", help="ProteinMPNN model name: v_48_002, v_48_010, v_48_020, v_48_030; v_48_010=version with 48 edges 0.10A noise")
argparser.add_argument("--seed", type=int, default=0, help="If set to 0 then a random seed will be picked;")
argparser.add_argument("--save_score", type=int, default=0, help="0 for False, 1 for True; save score=-log_prob to npy files")
argparser.add_argument("--save_probs", type=int, default=0, help="0 for False, 1 for True; save MPNN predicted probabilites per position")
argparser.add_argument("--score_only", type=int, default=0, help="0 for False, 1 for True; score input backbone-sequence pairs")
argparser.add_argument("--conditional_probs_only", type=int, default=0, help="0 for False, 1 for True; output conditional probabilities p(s_i given the rest of the sequence and backbone)")
argparser.add_argument("--conditional_probs_only_backbone", type=int, default=0, help="0 for False, 1 for True; if true output conditional probabilities p(s_i given backbone)")
argparser.add_argument("--unconditional_probs_only", type=int, default=0, help="0 for False, 1 for True; output unconditional probabilities p(s_i given backbone) in one forward pass")
argparser.add_argument("--backbone_noise", type=float, default=0.00, help="Standard deviation of Gaussian noise to add to backbone atoms")
argparser.add_argument("--num_seq_per_target", type=int, default=1, help="Number of sequences to generate per target")
argparser.add_argument("--batch_size", type=int, default=1, help="Batch size; can set higher for titan, quadro GPUs, reduce this if running out of GPU memory")
argparser.add_argument("--max_length", type=int, default=200000, help="Max sequence length")
argparser.add_argument("--sampling_temp", type=str, default="0.1", help="A string of temperatures, 0.2 0.25 0.5. Sampling temperature for amino acids. Suggested values 0.1, 0.15, 0.2, 0.25, 0.3. Higher values will lead to more diversity.")
argparser.add_argument("--out_folder", type=str, help="Path to a folder to output sequences, e.g. /home/out/")
argparser.add_argument("--pdb_path", type=str, default='', help="Path to a single PDB to be designed")
argparser.add_argument("--pdb_path_chains", type=str, default='', help="Define which chains need to be designed for a single PDB ")
argparser.add_argument("--jsonl_path", type=str, help="Path to a folder with parsed pdb into jsonl")
argparser.add_argument("--chain_id_jsonl",type=str, default='', help="Path to a dictionary specifying which chains need to be designed and which ones are fixed, if not specied all chains will be designed.")
argparser.add_argument("--fixed_positions_jsonl", type=str, default='', help="Path to a dictionary with fixed positions")
argparser.add_argument("--omit_AAs", type=list, default='X', help="Specify which amino acids should be omitted in the generated sequence, e.g. 'AC' would omit alanine and cystine.")
argparser.add_argument("--bias_AA_jsonl", type=str, default='', help="Path to a dictionary which specifies AA composion bias if neededi, e.g. {A: -1.1, F: 0.7} would make A less likely and F more likely.")
argparser.add_argument("--bias_by_res_jsonl", default='', help="Path to dictionary with per position bias.")
argparser.add_argument("--omit_AA_jsonl", type=str, default='', help="Path to a dictionary which specifies which amino acids need to be omited from design at specific chain indices")
argparser.add_argument("--pssm_jsonl", type=str, default='', help="Path to a dictionary with pssm")
argparser.add_argument("--pssm_multi", type=float, default=0.0, help="A value between [0.0, 1.0], 0.0 means do not use pssm, 1.0 ignore MPNN predictions")
argparser.add_argument("--pssm_threshold", type=float, default=0.0, help="A value between -inf + inf to restric per position AAs")
argparser.add_argument("--pssm_log_odds_flag", type=int, default=0, help="0 for False, 1 for True")
argparser.add_argument("--pssm_bias_flag", type=int, default=0, help="0 for False, 1 for True")
argparser.add_argument("--tied_positions_jsonl", type=str, default='', help="Path to a dictionary with tied positions")
For example to make a conda environment to run ProteinMPNN:
conda create --name mlfold- this creates conda environment calledmlfoldsource activate mlfold- this activate environmentconda install pytorch torchvision torchaudio cudatoolkit=11.3 -c pytorch- install pytorch following steps from https://pytorch.org/
These are provided examples/:
submit_example_1.sh- simple monomer examplesubmit_example_2.sh- simple multi-chain examplesubmit_example_3.sh- directly from the .pdb pathsubmit_example_3_score_only.sh- return score only (model's uncertainty)submit_example_4.sh- fix some residue positionssubmit_example_4_non_fixed.sh- specify which positions to designsubmit_example_5.sh- tie some positions together (symmetry)submit_example_6.sh- homooligomer examplesubmit_example_7.sh- return sequence unconditional probabilities (PSSM like)submit_example_8.sh- add amino acid bias
Output example:
>3HTN, score=1.1705, global_score=1.2045, fixed_chains=['B'], designed_chains=['A', 'C'], model_name=v_48_020, git_hash=015ff820b9b5741ead6ba6795258f35a9c15e94b, seed=37
NMYSYKKIGNKYIVSINNHTEIVKALNAFCKEKGILSGSINGIGAIGELTLRFFNPKTKAYDDKTFREQMEISNLTGNISSMNEQVYLHLHITVGRSDYSALAGHLLSAIQNGAGEFVVEDYSERISRTYNPDLGLNIYDFER/NMYSYKKIGNKYIVSINNHTEIVKALNAFCKEKGILSGSINGIGAIGELTLRFFNPKTKAYDDKTFREQMEISNLTGNISSMNEQVYLHLHITVGRSDYSALAGHLLSAIQNGAGEFVVEDYSERISRTYNPDLGLNIYDFER
>T=0.1, sample=1, score=0.7291, global_score=0.9330, seq_recovery=0.5736
NMYSYKKIGNKYIVSINNHTEIVKALKKFCEEKNIKSGSVNGIGSIGSVTLKFYNLETKEEELKTFNANFEISNLTGFISMHDNKVFLDLHITIGDENFSALAGHLVSAVVNGTCELIVEDFNELVSTKYNEELGLWLLDFEK/NMYSYKKIGNKYIVSINNHTDIVTAIKKFCEDKKIKSGTINGIGQVKEVTLEFRNFETGEKEEKTFKKQFTISNLTGFISTKDGKVFLDLHITFGDENFSALAGHLISAIVDGKCELIIEDYNEEINVKYNEELGLYLLDFNK
>T=0.1, sample=2, score=0.7414, global_score=0.9355, seq_recovery=0.6075
NMYKYKKIGNKYIVSINNHTEIVKAIKEFCKEKNIKSGTINGIGQVGKVTLRFYNPETKEYTEKTFNDNFEISNLTGFISTYKNEVFLHLHITFGKSDFSALAGHLLSAIVNGICELIVEDFKENLSMKYDEKTGLYLLDFEK/NMYKYKKIGNKYVVSINNHTEIVEALKAFCEDKKIKSGTVNGIGQVSKVTLKFFNIETKESKEKTFNKNFEISNLTGFISEINGEVFLHLHITIGDENFSALAGHLLSAVVNGEAILIVEDYKEKVNRKYNEELGLNLLDFNL
score- average over residues that were designed negative log probability of sampled amino acidsglobal score- average over all residues in all chains negative log probability of sampled/fixed amino acidsfixed_chains- chains that were not designed (fixed)designed_chains- chains that were redesignedmodel_name/CA_model_name- model name that was used to generate results, e.g.v_48_020git_hash- github version that was used to generate outputsseed- random seedT=0.1- temperature equal to 0.1 was used to sample sequencessample- sequence sample number 1, 2, 3...etc