Add rotamer libraries for phosphorated residues and functions to preserve original sidechains

.gitignore

@@ -2,6 +2,7 @@
 __pycache__/
 *.py[cod]
 *$py.class
+.DS_Store
 
 # C extensions
 *.so
@@ -112,3 +113,12 @@ venv.bak/
 
 # Dunbrack library files
 SimpleOpt1-5/
+
+# in development files
+src/mcsce/core/check_library.py
+src/mcsce/*.pdb
+src/mcsce/*_mcsce/
+src/mcsce/*.csv
+src/mcsce/test_pdbs/
+src/mcsce/core/data/glycam_06j.xml
+src/mcsce/core/sidechain_templates/cap_templates/

README.rst

@@ -20,7 +20,29 @@ MCSCE - Sidechain packing library
 Monte Carlo Side Chain Entropy package for generating side chain packing for
 fixed protein backbone.
 
-v0.0.0
+Updated supports for phosphorated residues and other listed modifications; other ptms in development.
+
+Phosphoralytion(unprotonated, protonated)
+
+- SER: SEP S1P 
+- THR: TPO T1P 
+- TYR: PTR Y1P 
+- HID: H2D H1D 
+- HIE: H2E H1E
+
+Methylation
+
+- LYS: M3L
+
+N6-carboxylysine
+
+- LYS: KCX
+
+Hydroxylation
+
+- PRO: HYP
+
+v0.1.0
 
 References
 ==========

src/mcsce/cli.py

@@ -2,7 +2,7 @@
 import os
 from datetime import datetime
 
-from numpy import mod
+from numpy import mod, any, array
 from tqdm.std import tqdm
 
 from mcsce.libs.libstructure import Structure
@@ -17,7 +17,9 @@
 parser.add_argument("-s", "--same_structure", action="store_true", default=False, help="When generating PDB files in a folder, whether each structure in the folder has the same amino acid sequence. When this is set to True, the energy function preparation will be done only once.")
 parser.add_argument("-b", "--batch_size", default=16, type=int, help="The batch size used for calculating energies for conformations. Consider decreasing batch size when encountered OOM in building.")
 parser.add_argument("-m", "--mode", choices=["ensemble", "simple", "exhaustive"], default="ensemble", help="This option controls whether a structural ensemble or just a single structure is created for every input structure. The default behavior is to create a structural ensemble. Simple/exhaustive modes are for creating single structure. In simple mode, n_conf structures are tried sequentially and the first valid structure is returned, and in exhaustive mode, a total number of n_conf structures will be created and the lowest energy conformation is returned.")
+parser.add_argument("-f", "--fix", default=None, help="list of residue ids whose side chains are retained. Specify start to stop (inclusive) with dash, and seperate id ranges with plus. E.g. 2-5+10-13. Only supports same structure mode and input structure should contain original side chains for residues to be fixed. Currently assumes continuous residue ids.")
 parser.add_argument("-l", "--logfile", default="log.csv", help="File name of the log file")
+parser.add_argument("-v", "--verbose", default=False, help="whether to print out warnings")
 
 
 def load_args(parser):
@@ -35,10 +37,10 @@ def maincli():
     """Independent client entry point."""
     cli(parser, main)
 
-def read_structure_and_check(file_name):
+def read_structure_and_check(file_name, retain_idx=[], verbose=False):
     """
     Helper function for reading a structure from a given filename and returns the structure object
-    Also checks whether there are missing atoms in the structure
+    checks whether there are missing atoms in the structure and 
     """
     s = Structure(file_name)
     s.build()
@@ -50,21 +52,27 @@ def read_structure_and_check(file_name):
         res_labels = s.res_labels
         res_labels[res_labels == "HIS"] = "HIP"
         s.res_labels = res_labels
-        print(message)
+        if verbose:
+            print(message)
+        else:
+            print("HIS residues modified to HIP\n")
     missing_backbone_atoms = s.check_backbone_atom_completeness()
     if len(missing_backbone_atoms) > 0:
         message = f"WARNING! These atoms are missing from the current backbone structure [{file_name}]:"
         for resid, atom_name in missing_backbone_atoms:
             message += f"\n{resid} {atom_name}"
-        print(message + "\n")
-    s = s.remove_side_chains()
+        if verbose:
+            print(message + "\n")
+        else:
+            print("WARNING! %d missing atoms in total"%(len(message.split("\n")) - 1))
+    s = s.remove_side_chains(retain_idx)
     return s
 
 
 
 
 
-def main(input_structure, n_conf, n_worker, output_dir, logfile, mode, batch_size=4, same_structure=False):
+def main(input_structure, n_conf, n_worker, output_dir, logfile, mode, fix, batch_size=4, same_structure=False, verbose=False):
 
     # antipattern to save time
     from mcsce.core.side_chain_builder import initialize_func_calc, create_side_chain_ensemble, create_side_chain
@@ -78,15 +86,26 @@ def main(input_structure, n_conf, n_worker, output_dir, logfile, mode, batch_siz
         f.write("PDB name,Succeeded,Time used\n")
 
     ff = forcefields["Amberff14SB"]
-    ff_obj = ff(add_OXT=True, add_Nterminal_H=True)
-
+    ff_obj = ff(Cterminal='OXT', Nterminal='HN')
+
+    if isinstance(fix, str):
+        if fix.find('-') + fix.find('+') <= -2 :
+            print('--fix argument syntax error. Abort')
+            return
+        elif not same_structure:
+            print('--fix argument ignored')
+    if not isinstance(fix, str) and fix is not None:
+         print('--fix argument syntax error. Abort')
+         return
+
     if n_worker is None:
         import multiprocessing
         n_worker = multiprocessing.cpu_count() - 1
     else:
         n_worker = n_worker
-    print("# workers:", n_worker)
-    print("mode: ", mode)
+    if verbose:
+        print("# workers:", n_worker)
+        print("mode: ", mode)
 
     if input_structure[-3:].upper() == "PDB":
         all_pdbs = [input_structure]
@@ -95,20 +114,49 @@ def main(input_structure, n_conf, n_worker, output_dir, logfile, mode, batch_siz
         if not input_folder.endswith("/"):
             input_folder += "/"
         all_pdbs = [input_folder + f for f in os.listdir(input_folder) if f[-3:].upper() == "PDB"]
-
+
+    fix_idxs = []
     if same_structure:
         # Assume all structures in a folder are the same: the energy creation step can be done only once
-        s = read_structure_and_check(all_pdbs[0])
+        s = Structure(all_pdbs[0])
+        s.build()
+        #print(s.data_array.shape, s._data_array.shape) 
+        if fix is not None:
+            fix = fix.strip()
+            if fix.find('-') == -1:
+                fix_idxs = [int(n) for n in fix.split('+')]
+            else:
+                if fix.find('+') == -1:
+                    fix_id_chunks = [fix]
+                else:
+                    fix_id_chunks = fix.split('+')
+                for chunk in fix_id_chunks:
+                    if chunk.find('-') == -1:
+                        fix_idxs += [int(chunk)]
+                    else:
+                        fix_range = [int(n) for n in chunk.split('-')]
+                        if len(fix_range) > 2:
+                            print('--fix argument syntax error. Abort')
+                            return
+                        start, stop = fix_range
+                        fix_idxs += list(range(start, stop+1))
+            if any(array(fix_idxs) > s.res_nums[-1]):
+                print('--fix residue id out of range')
+                return
+            # remove added sidechains in sections to be processed
+            s = s.remove_side_chains(fix_idxs)
+
         initialize_func_calc(partial(prepare_energy_function, batch_size=batch_size,
-         forcefield=ff_obj, terms=["lj", "clash"]),
-        structure=s)
+                   forcefield=ff_obj, terms=["lj", "clash", "coulomb"]),
+                   structure=s, retain_idxs=fix_idxs)
     if mode == "simple" and same_structure and n_worker > 1:
         # parallel executing sequential trials on the same structure (different conformations)
         t0 = datetime.now()
-        structures = [read_structure_and_check(f) for f in all_pdbs]
+        structures = [read_structure_and_check(f, fix_idxs, verbose) for f in all_pdbs]
         side_chain_parallel_creator = partial(create_side_chain, 
                                               n_trials=n_conf,
                                               temperature=300,
+                                              retain_resi=fix_idxs,
                                               parallel_worker=1,
                                               return_first_valid=True)
         import multiprocessing
@@ -142,26 +190,28 @@ def main(input_structure, n_conf, n_worker, output_dir, logfile, mode, batch_siz
                 output_dir = base_dir + "/" + os.path.splitext(os.path.basename(f))[0] + "_mcsce"
             if not os.path.exists(output_dir) and mode == "ensemble":
                 os.makedirs(output_dir)
-            s = read_structure_and_check(f)
+            s = read_structure_and_check(f, fix_idxs, verbose=verbose)
 
 
             if not same_structure:
                 initialize_func_calc(partial(prepare_energy_function, batch_size=batch_size,
-                forcefield=ff_obj, terms=["lj", "clash"]), structure=s)
+                forcefield=ff_obj, terms=["lj", "clash", "coulomb"]), structure=s)
 
             if mode == "ensemble":
                 conformations, success_indicator = create_side_chain_ensemble(
                     s,
                     n_conf,
                     temperature=300,
+                    retain_resi=fix_idxs,
                     save_path=output_dir,
                     parallel_worker=n_worker,
                     )
 
                 with open(logfile, "a") as _log:
                     _log.write("%s,%d,%s\n" % (f, sum(success_indicator), str(datetime.now() - t0)))
             else:
-                best_structure = create_side_chain(s, n_conf, 300, n_worker, mode=="simple")
+                best_structure = create_side_chain(s, n_conf, 300, parallel_worker=n_worker, 
+                                 retain_resi=fix_idxs, return_first_valid=(mode=="simple"))
                 if best_structure is not None:
                     best_structure.write_PDB(output_dir + ".pdb")
                     with open(logfile, "a") as _log: