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#! /usr/bin/python 

 

""" 

A python API and CLI to perform pKa calculations on peptides, 

proteins or lipid bilayers. 

""" 

 

import os 

 

import config as config 

from cli import checkParsedInput, readSettings, inputParametersFilter 

from cleaning import inputPDBCheck, cleanPDB 

from formats import convertTermini, pdb2gro 

import log as log 

 

from delphi4py import Delphi 

 

from molecule import Molecule 

from concurrency import startPoolProcesses, runDelPhiSims 

 

 

__author__ = "Pedro Reis" 

__version__ = "0.4" 

 

__email__ = "pdreis@fc.ul.pt" 

__status__ = "Development" 

 

 

def getTitrableSites(pdb): 

config.f_in = pdb 

config.params['ffID'] = 'G54A7' 

 

tit_mol = Molecule() 

 

tit_mol.makeSimpleSites() 

 

sites = tit_mol.getSitesOrdered() 

sites_keys = [] 

for site in sites: 

sitename = site.getName() 

sitenumber = site.getResNumber() 

sitenumber = convertTermini(sitenumber) 

if sitename in ('NTR', 'CTR'): 

if sitename == 'NTR': 

sites_keys.append('{0}N'.format(sitenumber)) 

else: 

sites_keys.append('{0}C'.format(sitenumber)) 

else: 

sites_keys.append(str(sitenumber)) 

 

return sites_keys 

 

 

class Titration(object): 

"""Main pypka class 

 

Serves as a wrapper to all other classes 

 

Attributes: 

_pKas: A dict with the calculated pKa values. 

""" 

def __init__(self, parameters, sites='all', debug=None, datfile=None): 

""" 

self._pKas = {} 

""" 

self._pKas = {} 

 

if sites: # None if from CLI 

parameters['sites_A'] = sites 

if sites != 'all': 

config.sites = sites 

else: 

config.sites = {} 

 

if datfile: 

config.f_dat = datfile 

parameters = readSettings(datfile) 

 

# Check Input Variables Validity 

inputParametersFilter(parameters) 

 

print 'Start Preprocessing' 

self.preprocessing() 

self.processDelPhiParams() 

 

print 'Start PB Calculations' 

 

self.DelPhiLaunch() 

print 'API exited successfully' 

 

def preprocessing(self): 

# Creating instance of TitratingMolecule 

config.tit_mole = Molecule() 

 

if config.f_in_extension == 'gro': 

groname = config.f_in 

if len(config.sites) > 0: 

chains_length, chains_res = inputPDBCheck(config.f_in, config.sites) 

config.tit_mole.loadSites(chains_length, chains_res) 

else: 

log.inputVariableError('sites', 

'defined.', 

'When using a .gro file format input is used, ' 

'sites needs to be defined') 

 

if config.f_in_extension == 'pdb': 

# Reading .st files 

# If the titrable residues are defined 

if len(config.sites) > 0: 

chains_length, chains_res = inputPDBCheck(config.f_in, config.sites) 

config.tit_mole.loadSites(chains_length, chains_res) 

# If the titrable residues are not defined and 

# the input pdb file is incomplete 

elif config.params['clean_pdb']: 

chains_res, sites = config.tit_mole.makeSimpleSites() 

# If the titrable residues are not defined and 

# the input pdb is not missing any atoms 

else: 

chains_res, sites = config.tit_mole.makeSimpleSites() 

config.tit_mole.deleteAllSites() 

config.tit_mole.makeSites(sites=sites) 

 

termini = {config.tit_mole._NTR: config.tit_mole._NTR_atoms, 

config.tit_mole._CTR: config.tit_mole._CTR_atoms} 

# Creates a .pdb input for DelPhi, where residues are in their standard state 

if config.params['clean_pdb']: 

inputpqr = 'clean.pqr' 

outputpqr = 'cleaned_tau.pqr' 

sites = config.tit_mole.getSites() 

site_numb_n_ref = {} 

for site in sites: 

site_numb_n_ref[site] = sites[site].getRefTautomerName() 

cleanPDB(config.f_in, config.pdb2pqr, chains_res, 

termini, config.userff, config.usernames, 

inputpqr, outputpqr, site_numb_n_ref) 

 

log.checkDelPhiErrors('LOG_addHtaut') 

config.tit_mole.deleteAllSites() 

config.tit_mole.makeSites(useTMPgro=True, sites=sites.keys()) 

else: 

pdb2gro(config.f_in, 'TMP.gro', config.tit_mole.box, config.sites, termini) 

groname = 'TMP.gro' 

 

config.tit_mole.readGROFile(groname) 

 

def processDelPhiParams(self): 

# Storing DelPhi parameters and Creates DelPhi data structures 

 

delphimol = Delphi(config.f_crg, config.f_siz, 'delphi_in_stmod.pdb', 

config.tit_mole.getNAtoms(), 

config.params['gsize'], 

config.params['scaleM'], 

config.params['precision'], 

epsin=config.params['epsin'], 

epsout=config.params['epssol'], 

conc=config.params['ionicstr'], 

ibctyp=config.params['bndcon'], 

res2=config.params['maxc'], 

nlit=config.params['nlit'], 

nonit=config.params['nonit'], 

relfac=0.0, 

relpar=0.0, 

pbx=config.params['pbx'], 

pby=config.params['pby'], 

debug=config.debug, outputfile='LOG_readFiles') 

 

log.checkDelPhiErrors('LOG_readFiles', 'readFiles') 

 

# Loads delphi4py object as TitratingMolecule attributes 

config.tit_mole.loadDelPhiParams(delphimol) 

 

if config.debug: 

config.tit_mole.printAllSites() 

config.tit_mole.printAllTautomers() 

print delphimol 

 

def DelPhiLaunch(self): 

if len(config.tit_mole.getSites()) < 1: 

raise Exception('At least one site has to be correctly defined.') 

 

# Runs DelPhi simulations for all tautomers 

results = startPoolProcesses(runDelPhiSims, 

config.tit_mole.iterAllSitesTautomers(), 

config.params['ncpus']) 

 

# Calculates the pKint of all tautomers 

config.tit_mole.calcpKint(results) 

 

# Calculates sites interaction energies and write .dat file 

config.tit_mole.calcSiteInteractionsParallel(config.params['ncpus']) 

 

# Monte Carlo sampling 

pKas, pmeans = config.tit_mole.runMC() 

 

sites = config.tit_mole.getSitesOrdered() 

 

c = -1 

for i in pKas: 

c += 1 

site = sites[c]._res_number 

pK = i[0] 

if pK != 100.0: 

self._pKas[site] = pK 

else: 

self._pKas[site] = '-' 

self._pmeans = pmeans 

 

def getAverageProt(self, site, pH): 

pKa = self[site] 

if type(pKa) == str: 

return 'pk Not In Range' 

average_prot = 10 ** (pKa - pH) / (1 + 10 ** (pKa - pH)) 

return average_prot 

 

def getProtState(self, site, pH): 

state = 'undefined' 

average_prot = self.getAverageProt(site, pH) 

 

if type(average_prot) == str: 

return state, average_prot 

 

if average_prot > 0.9: 

state = 'protonated' 

elif average_prot < 0.1: 

state = 'deprotonated' 

 

return state, average_prot 

 

def getTitration(self, site, pH='all'): 

site = self.correct_site_numb(site) 

pmeans = [] 

for pH in self._pmeans.keys(): 

self._pmeans[pH][site] 

 

def __iter__(self): 

self._iterpKas = [] 

for site in config.tit_mole.getSitesOrdered(): 

self._iterpKas.append(site.getResNumber()) 

self._iternumb = -1 

self._itermax = len(self._iterpKas) 

return self 

 

def next(self): 

self._iternumb += 1 

if self._iternumb < self._itermax: 

site = self._iterpKas[self._iternumb] 

if site > config.terminal_offset: 

if site - config.terminal_offset == config.tit_mole._NTR: 

site = 'NTR' 

elif site - config.terminal_offset == config.tit_mole._CTR: 

site = 'CTR' 

else: 

raise Exception('Something is terribly wrong') 

return site 

else: 

raise StopIteration 

 

def correct_site_numb(self, numb): 

if numb == 'NTR': 

numb = config.tit_mole._NTR + config.terminal_offset 

elif numb == 'CTR': 

numb = config.tit_mole._CTR + config.terminal_offset 

if type(numb) == str: 

try: 

numb = int(numb) 

except: 

raise Exception('Unknown site') 

return numb 

 

def __getitem__(self, numb): 

numb = self.correct_site_numb(numb) 

return self._pKas[numb] 

 

def __str__(self): 

output = ' Site Name pK' 

sites = config.tit_mole.getSites() 

 

for site in self._pKas: 

sitename = sites[site].getName() 

pk = self._pKas[site] 

if pk != '-': 

pk = round(pk, 2) 

else: 

pk = 'Not In Range' 

site = convertTermini(site) 

output += '\n{0:>6} {1:3} {2:>}'.format(site, 

sitename, pk) 

return output 

 

 

def CLI(): 

# Assignment of global variables 

parameters = checkParsedInput() 

Titration(parameters, sites=None) 

print 'CLI exited successfully' 

 

if __name__ == "__main__": 

CLI()