def _load_structures(inp, sys_params,): '''load protein/ligand structures needed for calculation''' parser = pdb.Big_PDBParser() print("now loading structures") # Read and/or create pickle files for the structures to save I/O time ligand_pkl_filename = os.path.join(inp['rootdir'], "ligand.pkl") receptor_pkl_filename = os.path.join(inp['rootdir'], "receptor.pkl") receptor_pkl_dry_filename = os.path.join(inp['rootdir'], "receptor_dry.pkl") receptor_pkl_dry_pqr_filename = os.path.join(inp['rootdir'], "receptor_dry_pqr.pkl") ligand=pickle_or_load(sys_params['lig_pqr_filename'], ligand_pkl_filename, struc_name="ligand", pqr=True) #receptor=pickle_or_load(sys_params['rec_pdb_filename'], receptor_pkl_filename, struc_name="receptor", pqr=False) receptor_dry=pickle_or_load(sys_params['rec_dry_pdb_filename'], receptor_pkl_dry_filename, struc_name="receptor_dry", pqr=False) receptor_dry_pqr=pickle_or_load(sys_params['rec_dry_pqr_filename'], receptor_pkl_dry_pqr_filename, struc_name="receptor_dry_pqr", pqr=True) struct={ # all parameters pertaining to structure 'ligand':ligand, #'receptor':receptor, 'receptor_dry':receptor_dry, # or create a function that will remove all waters, complicated by ions 'receptor_dry_pqr':receptor_dry_pqr, 'rec_com':pdb.center_of_mass(receptor_dry), # have to take into account the center of mass of the receptor itself 'lig_com':pdb.center_of_mass(ligand), # have to take into account the center of mass of the ligand itself } return struct
def _parse_pdb( filename, struct_name="pickle", ): parser = pdb.Big_PDBParser() struct = parser.get_structure(struct_name, filename, pqr=False, conventional=False) # load the file return struct
def pickle_or_load(filename, picklename, struc_name="pickle",pqr=False): '''for large files, instead of parsing, they can be saved and loaded much more quickly as a pickle. ''' parser = pdb.Big_PDBParser() if os.path.exists(picklename) and os.path.getmtime(picklename) > os.path.getmtime(filename): # if the pickle has been most recently modified # load the pickle print("reading pickle:", picklename) our_file=open(picklename, 'rb') our_obj=pickle.load(our_file) our_file.close() else: # then load the file itself and save the pickle our_obj=parser.get_structure(struc_name, filename, pqr=pqr, conventional=False) # load the file print("writing pickle:", picklename) our_file=open(picklename, 'wb') pickle.dump(our_obj, our_file, protocol=-1) our_file.close() return our_obj
import milestones import numpy as np import pdb2 as pdb from copy import deepcopy # needed to keep track of separate structure objects import namd_inputs # contains all the details for the namd input files import colvars import psfmerge #import MDAnalysis as mda #import * from adv_template import Adv_template, File_template import unittest import positions_orient import cPickle as pickle verbose = True parser = pdb.Big_PDBParser() self_path = os.path.dirname( os.path.realpath(__file__)) # get the path to this script fwd_rev_template_location = os.path.join(self_path, 'fwd_rev.template') def amber_building(settings): '''the pre-minimization procedure for amber ff simulations''' i = settings['index'] building = settings['md_file_paths'][i]['building'] working_pdb_base = 'holo' #settings['working_pdb_base'] pdbfile = settings['md_file_paths'][i]['wet_holo'] amber_settings = settings['amber_settings'] #sources=amber_settings['sources']
def build_bd(seekrcalc): ''' build all structures and necessary files for BD calculations takes a list of pqr filenames, reaction coordinate pairs/distances ''' if verbose: print '\n', '#'*40, "\n Now creating BD files using bd.py\n", '#'*40 parser = pdb.Big_PDBParser() rec_struct = parser.get_structure('bd_receptor_dry_pqr', seekrcalc.browndye.rec_dry_pqr_filename, pqr=True) #milestone_pos_rot_list = settings['milestone_pos_rot_list'] # NOTE: may want to clean up code referring to this variable ''' # TODO: marked for removal because feature probably not needed if settings['starting_conditions'] == 'configs': lig_configs = settings['lig_configs'] elif settings['starting_conditions'] == 'spheres': # then generate the anchors from random positions/orientations in a sphere # NOTE: there is a random orientation function in positions_orient.py pass else: raise Exception, "option not allowed: %s" % settings['starting_conditions'] ''' #bd_file_paths = settings['bd_file_paths'] #browndye_bin = settings['browndye_bin_dir'] #if not os.path.exists(empty_pqrxml) bd_configs = [] # fill the b_surface folder lig_config = seekrcalc.browndye.starting_lig_config # get the first config of the ligand lig_center = pdb.center_of_mass(lig_config) pqrs = [copy.deepcopy(rec_struct), copy.deepcopy(lig_config)] pqrs[1].struct_id='bd_ligand' #for site in settings['b_surface_ending_surfaces']: b_surface_criteria = [] starting_surfaces = [] for milestone in seekrcalc.milestones: if milestone.end: b_surface_criteria.append({'centerx':milestone.center_vec[0], 'centery':milestone.center_vec[1], 'centerz':milestone.center_vec[2], 'ligx':lig_center[0], 'ligy':lig_center[1], 'ligz':lig_center[2], 'radius':milestone.radius, 'index':milestone.index, 'siteid':milestone.siteid}) # add every site to the criteria list if milestone.bd: starting_surfaces.append({'site':milestone.siteid, 'radius':milestone.radius, 'index':milestone.index}) print "bsurface_criteria:", b_surface_criteria b_surface_pqrxmls = write_browndye_input(pqrs, seekrcalc, b_surface_criteria, work_dir=seekrcalc.browndye.b_surface_path, browndye_bin=seekrcalc.browndye.browndye_bin, start_at_site='false', fhpd_mode = False) # write input for this part ''' for bd_file_path in bd_file_paths: if not bd_file_path: pass #bd_configs.append(None) #continue # then don't do BD for this portion #print "bd_file_path:", bd_file_path anchor_folder_name = bd_file_path.split('/')[-2] # reading the file tree to get the index of every existing folder #print "anchor_folder_name:", anchor_folder_name folder_index = anchor_folder_name.split('_')[1] # getting the index out of the folder name bd_configs.append(int(folder_index)) ''' counter = 0 # the index of the loop itself for milestone in seekrcalc.milestones: if milestone.bd: lig_config = milestone.config bd_file_path = os.path.join(seekrcalc.project.rootdir, milestone.directory, 'bd') print "bd_file_path:", bd_file_path pqrs = [copy.deepcopy(rec_struct), copy.deepcopy(lig_config)] pqrs[1].struct_id='bd_ligand' bd_needed = True ''' m=0 for m in range(len(milestone_pos_rot_list)): # m will represent the proper milestone index if milestone_pos_rot_list[m][0].index == i: break ''' criteria = [] for surface in starting_surfaces: if surface['site'] == milestone.siteid: proper_radius = milestone.bd_adjacent.radius proper_index = milestone.bd_adjacent.index else: proper_radius = surface['radius'] proper_index = surface['index'] criteria.append({'centerx':milestone.center_vec[0], 'centery':milestone.center_vec[1], 'centerz':milestone.center_vec[2], 'ligx':lig_center[0], 'ligy':lig_center[1], 'ligz':lig_center[2], 'radius':proper_radius, 'index':proper_index, 'siteid':milestone.siteid}) ''' criteria = [] #[[(31.121, 37.153, 35.253), (38.742, 51.710, 68.137), 9.0],] # a list of all reaction criteria for site in settings['starting_surfaces']: #site_center = [site['x'], site['y'],site['z']] #radius = site['radius'] # NOTE: at this time, only spherical reaction criteria are allowed in BrownDye if milestone_pos_rot_list[m][0].siteid == site['siteid']: # then its the same site, we need to go one shell in proper_radius = site['inner_radius'] # the radius in the same site proper_index = site['inner_index'] else: # this is a different site, choose the same radius as starting proper_radius = site['outer_radius'] proper_index = site['outer_index'] criteria.append({'centerx':site['x'], 'centery':site['y'], 'centerz':site['z'], 'ligx':lig_center[0], 'ligy':lig_center[1], 'ligz':lig_center[2], 'radius':proper_radius, 'index':proper_index, 'siteid':site['siteid']}) # add every site to the criteria list ''' #print "pqrs:", pqrs, 'criteria:', criteria site_pqrxmls = write_browndye_input(pqrs, seekrcalc, criteria, work_dir=bd_file_path, browndye_bin=seekrcalc.browndye.browndye_bin,fhpd_mode=True) # make BD preparation scripts extract_bd_frames.py and bd_fhpd.pyp # Write the script to extract all frames from the successful b_surface bd trajectories extract_bd_frames_dict = {'TRAJDIR':"../../b_surface", 'WORKDIR':"./trajs", 'PQRXML0':os.path.basename(b_surface_pqrxmls[0]), 'PQRXML1':os.path.basename(b_surface_pqrxmls[1]), 'EMPTY':empty_pqrxml, 'SITENAME':'%s_%s' % (milestone.siteid, milestone.index), 'NUMBER_OF_TRAJS':seekrcalc.browndye.num_threads} extract_bd_frames = Adv_template(extract_bd_frames_template, extract_bd_frames_dict) extract_file = open(os.path.join(bd_file_path,"extract_bd_frames.py"), 'w') extract_file.write(extract_bd_frames.get_output()) # write an xml file for the input to bd extract_file.close() # construct the FHPD distribution prep scripts make_fhpd_dict = {'INPUT_TEMPLATE_FILENAME':'input.xml', 'RECEPTOR_PQRXML':os.path.basename(b_surface_pqrxmls[0]), 'RXNS':'rxns.xml', 'NTRAJ':seekrcalc.browndye.fhpd_numtraj, 'ARGS':"glob.glob(os.path.join('./trajs','lig*.pqr'))"} # NOTE: should change NTRAJ to be consistent with the number of reaction events in the b_surface phase make_fhpd = Adv_template(make_fhpd_template,make_fhpd_dict) make_fhpd_file = open(os.path.join(bd_file_path,"make_fhpd.py"), 'w') make_fhpd_file.write(make_fhpd.get_output()) # write an xml file for the input to bd make_fhpd_file.close() # Consolidate all result files from the FHPD simulations into one large results.xml file fhpd_consolidate_dict = {'FHPD_DIR':"fhpd", 'LIG_DIR_GLOB':"lig*/", 'RESULTS_NAME':'results.xml'} fhpd_consolidate = Adv_template(fhpd_consolidate_template,fhpd_consolidate_dict) fhpd_consolidate_file = open(os.path.join(bd_file_path,"fhpd_consolidate.py"), 'w') fhpd_consolidate_file.write(fhpd_consolidate.get_output()) # write an xml file for the input to bd fhpd_consolidate_file.close() make_empty_pqrxml(os.path.join(bd_file_path, 'empty.pqrxml')) counter += 1
def generate_configs(seekrcalc): '''Generates the apo and holo configurations of the receptors and ligands. Input: - seekrcalc: a SeekrCalculation() object that contains all the settings for the SEEKR calculation Output: - None ''' if verbose: print "Generating structural configurations..." parser = pdb.Big_PDBParser() if verbose: print "now loading structures" # Read and/or create pickle files for the structures to save I/O time ligand_pkl_filename = os.path.join(seekrcalc.project.rootdir, "ligand.pkl") receptor_pkl_wet_filename = os.path.join(seekrcalc.project.rootdir, "receptor.pkl") #receptor_pkl_dry_filename = os.path.join(seekrcalc.project.rootdir, "receptor_dry.pkl") receptor_pkl_dry_pqr_filename = os.path.join(seekrcalc.project.rootdir, "receptor_dry_pqr.pkl") ligand = pickle_or_load(seekrcalc.building.lig_dry_pqr_filename, ligand_pkl_filename, parser, struc_name="ligand", pqr=True) receptor_wet = pickle_or_load(seekrcalc.building.rec_wet_pdb_filename, receptor_pkl_wet_filename, parser, struc_name="receptor_wet", pqr=False) receptor_dry = pickle_or_load(seekrcalc.building.rec_dry_pqr_filename, receptor_pkl_dry_pqr_filename, parser, struc_name="receptor_dry_pqr", pqr=True) seekrcalc.building.ligand = ligand seekrcalc.building.rec_wet_pdb_filename = receptor_wet seekrcalc.building.rec_dry_pqr_filename = receptor_dry milestones = seekrcalc.milestones configs = [] starttime = time.time() struct_center = pdb.center_of_mass(ligand) if verbose: print "Generating", len(milestones), "ligand configurations" for milestone in milestones: new_ligand = deepcopy(ligand) # copy the entire structure new_ligand.moveby( -struct_center) # reposition ligand structure over the origin new_ligand.moveby( milestone.anchor) # move ligand to the anchor location new_ligand.struct_id = milestone.fullname configs.append(new_ligand) endtime = time.time() if verbose: "Generate_configs complete. Total number: %d. Elapsed time: %d s" % ( len(configs), endtime - starttime, ) print "Now running through all configurations to combine ligand with receptor." if seekrcalc.building.reject_clashes: print "Rejecting steric clashes..." else: print "Ignoring steric clashes..." if seekrcalc.project.bd: seekrcalc.browndye.starting_lig_config = configs[0] for i, milestone in enumerate( milestones): # run thru all the configurations of ligands lig_config = configs[i] milestone.config = deepcopy(lig_config) if seekrcalc.building.reject_clashes: if structures_clash(lig_config, receptor_dry, tolerance=0.2): continue # if there's a clash if milestone.md: #pdb.TER_resnames.append(seekrcalc.building.lig_resname) # TODO: marked for removal holo_config_wet, insert_index, last_ligand_index = pdb.ligmerge( lig_config, receptor_wet, verbose=False) holo_config_wet.struct_id = lig_config.struct_id # set the structure description to the same as the ligand holo_config_wet.renumber_indeces( ) # to number the indeces consecutively wet_holo_filename = milestone.openmm.wet_holo_pdb_filename if verbose: print "writing file:", wet_holo_filename holo_config_wet.save( wet_holo_filename, amber=True, standard=False ) # write the holo structure into the md directory last_insert_index = insert_index last_last_ligand_index = last_ligand_index if milestone.bd: holo_config_dry, insert_index, last_ligand_index = pdb.ligmerge( lig_config, receptor_dry, verbose=False) holo_config_dry.struct_id = lig_config.struct_id # set the structure description to the same as the ligand holo_config_dry.renumber_indeces( ) # to number the indeces consecutively dry_holo_filename = milestone.openmm.dry_holo_pdb_filename if verbose: print "writing file:", dry_holo_filename holo_config_dry.save( dry_holo_filename, amber=True, standard=False ) # write the holo structure into the md directory return holo_config_wet, last_insert_index, last_last_ligand_index