#! /usr/bin/env python
"""
Protein-Ligand Interaction Profiler - Analyze and visualize protein-ligand interactions in PDB files.
plipcmd.py - Main script for PLIP command line execution.
"""

# system imports
import argparse
import logging
import multiprocessing
import os
import sys
from argparse import ArgumentParser
from collections import namedtuple

from plip.basic import config, logger

logger = logger.get_logger()

from plip.basic.config import __version__
from plip.basic.parallel import parallel_fn
from plip.basic.remote import VisualizerData
from plip.exchange.report import StructureReport
from plip.exchange.webservices import fetch_pdb
from plip.structure.preparation import create_folder_if_not_exists, extract_pdbid
from plip.structure.preparation import tilde_expansion, PDBComplex

description = f"The Protein-Ligand Interaction Profiler (PLIP) {__version__}" \
              "is a command-line based tool to analyze interactions in a protein-ligand complex. " \
              "If you are using PLIP in your work, please cite: " \
              "Salentin,S. et al. PLIP: fully automated protein-ligand interaction profiler. " \
              "Nucl. Acids Res. (1 July 2015) 43 (W1): W443-W447. doi:10.1093/nar/gkv315" \
              f"Supported and maintained by: {config.__maintainer__}"


def threshold_limiter(aparser, arg):
    arg = float(arg)
    if arg <= 0:
        aparser.error("All thresholds have to be values larger than zero.")
    return arg


def process_pdb(pdbfile, outpath, as_string=False, outputprefix='report'):
    """Analysis of a single PDB file. Can generate textual reports XML, PyMOL session files and images as output."""
    if not as_string:
        pdb_file_name = pdbfile.split('/')[-1]
        startmessage = f'starting analysis of {pdb_file_name}'
    else:
        startmessage = 'starting analysis from STDIN'
    logger.info(startmessage)
    mol = PDBComplex()
    mol.output_path = outpath
    mol.load_pdb(pdbfile, as_string=as_string)
    # @todo Offers possibility for filter function from command line (by ligand chain, position, hetid)
    for ligand in mol.ligands:
        mol.characterize_complex(ligand)

    create_folder_if_not_exists(outpath)

    # Generate the report files
    streport = StructureReport(mol, outputprefix=outputprefix)

    config.MAXTHREADS = min(config.MAXTHREADS, len(mol.interaction_sets))

    ######################################
    # PyMOL Visualization (parallelized) #
    ######################################

    if config.PYMOL or config.PICS:
        from plip.visualization.visualize import visualize_in_pymol
        complexes = [VisualizerData(mol, site) for site in sorted(mol.interaction_sets)
                     if not len(mol.interaction_sets[site].interacting_res) == 0]
        if config.MAXTHREADS > 1:
            logger.info(f'generating visualizations in parallel on {config.MAXTHREADS} cores')
            parfn = parallel_fn(visualize_in_pymol)
            parfn(complexes, processes=config.MAXTHREADS)
        else:
            [visualize_in_pymol(plcomplex) for plcomplex in complexes]

    if config.XML:  # Generate report in xml format
        streport.write_xml(as_string=config.STDOUT)

    if config.TXT:  # Generate report in txt (rst) format
        streport.write_txt(as_string=config.STDOUT)


def download_structure(inputpdbid):
    """Given a PDB ID, downloads the corresponding PDB structure.
    Checks for validity of ID and handles error while downloading.
    Returns the path of the downloaded file."""
    try:
        if len(inputpdbid) != 4 or extract_pdbid(inputpdbid.lower()) == 'UnknownProtein':
            logger.error(f'invalid PDB-ID (wrong format): {inputpdbid}')
            sys.exit(1)
        pdbfile, pdbid = fetch_pdb(inputpdbid.lower())
        pdbpath = tilde_expansion('%s/%s.pdb' % (config.BASEPATH.rstrip('/'), pdbid))
        create_folder_if_not_exists(config.BASEPATH)
        with open(pdbpath, 'w') as g:
            g.write(pdbfile)
        logger.info(f'file downloaded as {pdbpath}')
        return pdbpath, pdbid

    except ValueError:  # Invalid PDB ID, cannot fetch from RCBS server
        logger.error(f'PDB-ID does not exist: {inputpdbid}')
        sys.exit(1)


def remove_duplicates(slist):
    """Checks input lists for duplicates and returns
    a list with unique entries"""
    unique = list(set(slist))
    difference = len(slist) - len(unique)
    if difference == 1:
        logger.info('removed one duplicate entry from input list')
    if difference > 1:
        logger.info(f'Removed {difference} duplicate entries from input list')
    return unique


def run_analysis(inputstructs, inputpdbids):
    """Main function. Calls functions for processing, report generation and visualization."""
    pdbid, pdbpath = None, None
    # @todo For multiprocessing, implement better stacktracing for errors
    # Print title and version
    logger.info(f'Protein-Ligand Interaction Profiler (PLIP) {__version__}')
    logger.info(f'brought to you by: {config.__maintainer__}')
    logger.info(f'please cite: https://www.doi.org/10.1093/nar/gkv315')
    output_prefix = config.OUTPUTFILENAME

    if inputstructs is not None:  # Process PDB file(s)
        num_structures = len(inputstructs)
        inputstructs = remove_duplicates(inputstructs)
        read_from_stdin = False
        for inputstruct in inputstructs:
            if inputstruct == '-':
                inputstruct = sys.stdin.read()
                read_from_stdin = True
                if config.RAWSTRING:
                    if sys.version_info < (3,):
                        inputstruct = bytes(inputstruct).decode('unicode_escape')
                    else:
                        inputstruct = bytes(inputstruct, 'utf8').decode('unicode_escape')
            else:
                if os.path.getsize(inputstruct) == 0:
                    logger.error('empty PDB file')
                    sys.exit(1)
                if num_structures > 1:
                    basename = inputstruct.split('.')[-2].split('/')[-1]
                    config.OUTPATH = '/'.join([config.BASEPATH, basename])
                    output_prefix = 'report'
            process_pdb(inputstruct, config.OUTPATH, as_string=read_from_stdin, outputprefix=output_prefix)
    else:  # Try to fetch the current PDB structure(s) directly from the RCBS server
        num_pdbids = len(inputpdbids)
        inputpdbids = remove_duplicates(inputpdbids)
        for inputpdbid in inputpdbids:
            pdbpath, pdbid = download_structure(inputpdbid)
            if num_pdbids > 1:
                config.OUTPATH = '/'.join([config.BASEPATH, pdbid[1:3].upper(), pdbid.upper()])
                output_prefix = 'report'
            process_pdb(pdbpath, config.OUTPATH, outputprefix=output_prefix)

    if (pdbid is not None or inputstructs is not None) and config.BASEPATH is not None:
        if config.BASEPATH in ['.', './']:
            logger.info('finished analysis, find the result files in the working directory')
        else:
            logger.info(f'finished analysis, find the result files in {config.BASEPATH}')


if __name__ == '__main__':
    """Parse command line arguments and start main script for analysis."""
    parser = ArgumentParser(prog="PLIP", description=description)
    pdbstructure = parser.add_mutually_exclusive_group(required=True)  # Needs either PDB ID or file
    # '-' as file name reads from stdin
    pdbstructure.add_argument("-f", "--file", dest="input", nargs="+", help="Set input file, '-' reads from stdin")
    pdbstructure.add_argument("-i", "--input", dest="pdbid", nargs="+")
    outputgroup = parser.add_mutually_exclusive_group(required=False)  # Needs either outpath or stdout
    outputgroup.add_argument("-o", "--out", dest="outpath", default="./")
    outputgroup.add_argument("-O", "--stdout", dest="stdout", action="store_true", default=False,
                             help="Write to stdout instead of file")
    parser.add_argument("--rawstring", dest="use_raw_string", default=False, action="store_true",
                        help="Use Python raw strings for stdout and stdin")
    parser.add_argument("-v", "--verbose", dest="verbose", default=False, help="Turn on verbose mode",
                        action="store_true")
    parser.add_argument("-q", "--quiet", dest="quiet", default=False, help="Turn on quiet mode", action="store_true")
    parser.add_argument("-s", "--silent", dest="silent", default=False, help="Turn on silent mode", action="store_true")
    parser.add_argument("-p", "--pics", dest="pics", default=False, help="Additional pictures", action="store_true")
    parser.add_argument("-x", "--xml", dest="xml", default=False, help="Generate report file in XML format",
                        action="store_true")
    parser.add_argument("-t", "--txt", dest="txt", default=False, help="Generate report file in TXT (RST) format",
                        action="store_true")
    parser.add_argument("-y", "--pymol", dest="pymol", default=False, help="Additional PyMOL session files",
                        action="store_true")
    parser.add_argument("--maxthreads", dest="maxthreads", default=multiprocessing.cpu_count(),
                        help="Set maximum number of main threads (number of binding sites processed simultaneously)."
                             "If not set, PLIP uses all available CPUs if possible.",
                        type=int)
    parser.add_argument("--breakcomposite", dest="breakcomposite", default=False,
                        help="Don't combine ligand fragments with covalent bonds but treat them as single ligands for the analysis.",
                        action="store_true")
    parser.add_argument("--altlocation", dest="altlocation", default=False,
                        help="Also consider alternate locations for atoms (e.g. alternate conformations).",
                        action="store_true")
    parser.add_argument("--nofix", dest="nofix", default=False,
                        help="Turns off fixing of PDB files.",
                        action="store_true")
    parser.add_argument("--nofixfile", dest="nofixfile", default=False,
                        help="Turns off writing files for fixed PDB files.",
                        action="store_true")
    parser.add_argument("--nopdbcanmap", dest="nopdbcanmap", default=False,
                        help="Turns off calculation of mapping between canonical and PDB atom order for ligands.",
                        action="store_true")
    parser.add_argument("--dnareceptor", dest="dnareceptor", default=False,
                        help="Uses the DNA instead of the protein as a receptor for interactions.",
                        action="store_true")
    parser.add_argument("--name", dest="outputfilename", default="report",
                        help="Set a filename for the report TXT and XML files. Will only work when processing single structures.")
    ligandtype = parser.add_mutually_exclusive_group()  # Either peptide/inter or intra mode
    ligandtype.add_argument("--peptides", "--inter", dest="peptides", default=[],
                            help="Allows to define one or multiple chains as peptide ligands or to detect inter-chain contacts",
                            nargs="+")
    ligandtype.add_argument("--intra", dest="intra", help="Allows to define one chain to analyze intra-chain contacts.")
    parser.add_argument("--keepmod", dest="keepmod", default=False,
                        help="Keep modified residues as ligands",
                        action="store_true")
    parser.add_argument("--nohydro", dest="nohydro", default=False,
                        help="Do not add polar hydrogens in case your structure already contains hydrogens.",
                        action="store_true")
    # Optional threshold arguments, not shown in help
    thr = namedtuple('threshold', 'name type')
    thresholds = [thr(name='aromatic_planarity', type='angle'),
                  thr(name='hydroph_dist_max', type='distance'), thr(name='hbond_dist_max', type='distance'),
                  thr(name='hbond_don_angle_min', type='angle'), thr(name='pistack_dist_max', type='distance'),
                  thr(name='pistack_ang_dev', type='other'), thr(name='pistack_offset_max', type='distance'),
                  thr(name='pication_dist_max', type='distance'), thr(name='saltbridge_dist_max', type='distance'),
                  thr(name='halogen_dist_max', type='distance'), thr(name='halogen_acc_angle', type='angle'),
                  thr(name='halogen_don_angle', type='angle'), thr(name='halogen_angle_dev', type='other'),
                  thr(name='water_bridge_mindist', type='distance'), thr(name='water_bridge_maxdist', type='distance'),
                  thr(name='water_bridge_omega_min', type='angle'), thr(name='water_bridge_omega_max', type='angle'),
                  thr(name='water_bridge_theta_min', type='angle')]
    for t in thresholds:
        parser.add_argument('--%s' % t.name, dest=t.name, type=lambda val: threshold_limiter(parser, val),
                            help=argparse.SUPPRESS)

    arguments = parser.parse_args()

    # configure log levels
    config.VERBOSE = True if arguments.verbose else False
    config.QUIET = True if arguments.quiet else False
    config.SILENT = True if arguments.silent else False
    if config.VERBOSE:
        logger.setLevel(logging.DEBUG)
    elif config.QUIET:
        logger.setLevel(logging.WARN)
    elif config.SILENT:
        logger.setLevel(logging.CRITICAL)
    else:
        logger.setLevel(config.DEFAULT_LOG_LEVEL)

    config.MAXTHREADS = arguments.maxthreads
    config.XML = arguments.xml
    config.TXT = arguments.txt
    config.PICS = arguments.pics
    config.PYMOL = arguments.pymol
    config.STDOUT = arguments.stdout
    config.RAWSTRING = arguments.use_raw_string
    config.OUTPATH = arguments.outpath
    config.OUTPATH = tilde_expansion("".join([config.OUTPATH, '/'])
                                     if not config.OUTPATH.endswith('/') else config.OUTPATH)
    config.BASEPATH = config.OUTPATH  # Used for batch processing
    config.BREAKCOMPOSITE = arguments.breakcomposite
    config.ALTLOC = arguments.altlocation
    config.PEPTIDES = arguments.peptides
    config.INTRA = arguments.intra
    config.NOFIX = arguments.nofix
    config.NOFIXFILE = arguments.nofixfile
    config.NOPDBCANMAP = arguments.nopdbcanmap
    config.KEEPMOD = arguments.keepmod
    config.DNARECEPTOR = arguments.dnareceptor
    config.OUTPUTFILENAME = arguments.outputfilename
    config.NOHYDRO = arguments.nohydro
    # Make sure we have pymol with --pics and --pymol
    if config.PICS or config.PYMOL:
        try:
            import pymol
        except ImportError:
            logger.error('PyMOL is required for the --pics and --pymol option')
            sys.exit(1)
    # Assign values to global thresholds
    for t in thresholds:
        tvalue = getattr(arguments, t.name)
        if tvalue is not None:
            if t.type == 'angle' and not 0 < tvalue < 180:  # Check value for angle thresholds
                parser.error("Threshold for angles need to have values within 0 and 180.")
            if t.type == 'distance':
                if tvalue > 10:  # Check value for angle thresholds
                    parser.error("Threshold for distances must not be larger than 10 Angstrom.")
                elif tvalue > config.BS_DIST + 1:  # Dynamically adapt the search space for binding site residues
                    config.BS_DIST = tvalue + 1
            setattr(config, t.name.upper(), tvalue)
    # Check additional conditions for interdependent thresholds
    if not config.HALOGEN_ACC_ANGLE > config.HALOGEN_ANGLE_DEV:
        parser.error("The halogen acceptor angle has to be larger than the halogen angle deviation.")
    if not config.HALOGEN_DON_ANGLE > config.HALOGEN_ANGLE_DEV:
        parser.error("The halogen donor angle has to be larger than the halogen angle deviation.")
    if not config.WATER_BRIDGE_MINDIST < config.WATER_BRIDGE_MAXDIST:
        parser.error("The water bridge minimum distance has to be smaller than the water bridge maximum distance.")
    if not config.WATER_BRIDGE_OMEGA_MIN < config.WATER_BRIDGE_OMEGA_MAX:
        parser.error("The water bridge omega minimum angle has to be smaller than the water bridge omega maximum angle")
    expanded_path = tilde_expansion(arguments.input) if arguments.input is not None else None
    run_analysis(expanded_path, arguments.pdbid)  # Start main script