def get_final_score(data_dir):
'''
1. run iAlign, -> structure_align.out
2. run PSI-BLAST, -> sequence_align.out
3. get SSIP score, -> ssip_score.txt
4. run EvoEF, -> evoef_score.txt
5. get final score -> result.txt
'''
#### make temporary directory ####
tmp_dir = "/tmp/" + os.getenv("USER") + "/" + os.path.basename(data_dir)
if os.path.isdir(tmp_dir):
shutil.rmtree(tmp_dir)
os.makedirs(tmp_dir)
#### parse input files ####
isscore = "0.5"
force_field = "SSIPE" # SSIPe force field by default
isscore_file = os.path.join(data_dir, "isscore")
force_field_file = os.path.join(data_dir, "force_field")
pdb_file = os.path.join(data_dir, "complex.pdb")
seq_file = os.path.join(data_dir, "seq.fasta")
mutlist_file = os.path.join(data_dir, "mutList.txt")
align_file1 = os.path.join(data_dir, "structure_align.out")
align_file2 = os.path.join(data_dir, "sequence_align.out")
ssipscore_file = os.path.join(data_dir, "ssip_score.txt")
evoefscore_file = os.path.join(data_dir, "evoef_score.txt")
result_file = os.path.join(data_dir, "result.txt")
if os.path.isfile(isscore_file):
fp = open(isscore_file, 'rU')
isscore = fp.read().strip()
fp.close()
if os.path.isfile(force_field_file):
fp = open(force_field_file, 'rU')
force_field = fp.read().strip()
fp.close()
#### define temporary files ####
pdb_tmp = os.path.join(tmp_dir, "complex.pdb")
seq_tmp = os.path.join(tmp_dir, "seq.fasta")
align_tmp1 = os.path.join(tmp_dir, "structure_align.out")
align_tmp2 = os.path.join(tmp_dir, "sequence_align.out")
mutlist_tmp = os.path.join(tmp_dir, "mutList.txt")
ssipscore_tmp = os.path.join(tmp_dir, "ssip_score.txt")
evoefscore_tmp = os.path.join(tmp_dir, "evoef_score.txt")
#### renumber residue index and output the files to temporary folder ####
#resi_dict,inv_resi_dict=reindex_complex(mutlist_file,pdb_file,mutlist_tmp,pdb_tmp)
shutil.copy(mutlist_file, mutlist_tmp)
shutil.copy(pdb_file, pdb_tmp)
#### interface alignment ####
sys.stdout.write("step 1: run iAlign\n")
if os.path.isfile(align_file1):
shutil.copy(align_file1, align_tmp1)
else:
newscore = max(float(isscore), 0.45)
newscore = min(newscore, 0.55)
isscore = str(newscore)
cmd = ' '.join([
"cd", tmp_dir, ';', run_align, pdb_tmp,
str(newscore), align_tmp1
])
os.system(cmd)
align_file1 = os.path.join(data_dir, "structure_align.out")
shutil.copy(align_tmp1, align_file1)
#### fix insertion code in align.out ####
fp = open(align_tmp1, 'rU')
lines = fp.read().splitlines()
fp.close()
txt = ''
insert_code_pattern = re.compile("\d+[A-Za-z]")
for line in lines:
if not line.startswith("residue_") or not insert_code_pattern.search(
line):
txt += line + '\n'
else:
for resi in line.split(' '):
if resi == '':
txt += ' '
elif not insert_code_pattern.match(resi):
txt += resi
else:
txt += ' ' + resi[:-1]
txt += '\n'
fp = open(align_tmp1, 'w')
fp.write(txt)
fp.close()
#### run psiblast to get sequence interface alignment ####
sys.stdout.write("step 2: run psiblast\n")
if (os.path.isfile(align_tmp1)):
if (os.path.isfile(align_file2)):
shutil.copy(align_file2, align_tmp2)
else:
cmd = ' '.join([
"cd", tmp_dir, ";", run_seqalign, pdb_tmp, align_tmp1,
align_tmp2
])
os.system(cmd)
align_file2 = os.path.join(data_dir, "sequence_align.out")
shutil.copy(align_tmp2, align_file2)
else:
sys.stdout.write(
"step 2: skip psiblast because iAlign alignment file doesn't exist"
)
#### get SSIP score ####
sys.stdout.write("step 3: get_ssip_score\n")
if (os.path.isfile(align_tmp1) or os.path.isfile(align_tmp2)):
cmd = ' '.join([
"cd", tmp_dir, ';', get_ssip_score, mutlist_tmp, align_tmp1,
align_tmp2, isscore, ssipscore_tmp
])
os.system(cmd)
shutil.copy(ssipscore_tmp, ssipscore_file)
#copy the sorted file back to the data_dir
shutil.copy(align_tmp1, align_file1)
shutil.copy(align_tmp2, align_file2)
else:
sys.stdout.write(
"step 3: skip get_ssip_score because structure_align.out and sequence_align.out don't exist"
)
#### get evoef score ####
sys.stdout.write("step 4: get_evoef_score\n")
if force_field == "SSIPE":
if os.path.isfile(evoefscore_file):
shutil.copy(evoefscore_file, evoefscore_tmp)
else:
#shutil.copy(pdb_file,pdb_tmp)
cmd = ' '.join([
"cd", tmp_dir, ';', run_evoef, pdb_tmp, mutlist_tmp,
evoefscore_tmp
])
os.system(cmd)
shutil.copy(evoefscore_tmp, evoefscore_file)
#### get final score ####
sys.stdout.write("step 5: get_final_score\n")
fp = open(mutlist_file, 'rU')
mutation_list = fp.read().strip().splitlines()
fp.close()
fp = open(ssipscore_tmp, 'rU')
ssipscore_list = [float(l) for l in fp.read().splitlines()]
fp.close()
finalscore_list = []
if os.path.isfile(evoefscore_tmp):
fp = open(evoefscore_tmp, 'rU')
evoefscore_list = [float(f) for f in fp.read().splitlines()]
fp.close()
for x, f, m in zip(ssipscore_list, evoefscore_list, mutation_list):
if x == 0. and f == 0.:
finalscore_list.append(0.)
else:
finalscore_list.append(0.734 * x + 0.341 * f + 0.205)
#finalscore_list=[0.74*x+0.33*f+0.26 for x,f,m in \
# zip(ssipscore_list,evoefscore_list,mutation_list)]
else:
finalscore_list = ssipscore_list
result_list = [
"%-7.3f %-9.3f %-10.3f %s" % (f, s, e, m) for f, s, e, m in zip(
finalscore_list, ssipscore_list, evoefscore_list, mutation_list)
]
fp = open(result_file, 'w')
fp.write('DDG SSIPscore EvoEFscore mutations\n')
fp.write('\n'.join(result_list) + '\n')
fp.close()
#### copy mutant PDB structure if available ####
for mutation in mutation_list:
mutant_file = os.path.join(
data_dir,
"complex_" + mutation.rstrip(';').replace(',', '_') + ".pdb")
mutant_tmp = os.path.join(
tmp_dir,
"complex_" + mutation.rstrip(';').replace(',', '_') + ".pdb")
if os.path.isfile(mutant_tmp):
shutil.copy(mutant_tmp, mutant_file)
cmd = ' '.join([
"cd", tmp_dir, ";",
"tar -jcvf mutation_structures.tar.bz2 complex_*.pdb"
])
os.system(cmd)
shutil.copy(os.path.join(tmp_dir, "mutation_structures.tar.bz2"),
os.path.join(data_dir, "mutation_structures.tar.bz2"))
#get chain list
header_list, sequence_list = pdb2seq(pdb_file)
chain_list = [h.split(':')[-1] for h in header_list]
#### extract interface PDB file ####
cmd = ' '.join([
extint, "-s", pdb_file, "-r", chain_list[0], "-l", chain_list[1], "-c",
os.path.join(data_dir, "contact.list"), "-i",
os.path.join(data_dir, "interface.pdb")
])
os.system(cmd)
#### make html output ####
sys.stdout.write("step 6: index.html\n")
#make_webpage(inv_resi_dict,data_dir,isscore,force_field,result_list)
make_webpage(data_dir, isscore, force_field, result_list)
#### clean up temporary directory ####
shutil.rmtree(tmp_dir)
return
def make_webpage(data_dir, isscore, force_field, result_list):
'''make index.html for data folder "data_dir".'''
html_template = Template("""<html>
<head><meta http-equiv="content-type" content="text/html; charset=UTF-8">
<title>SSIPe job finished</title></head>
<body>
[<a href="$HTTP_LINK">back to SSIPe server</a>]<br/>
<h1 align="center">SSIPe job id $JOBID</h1>
<div style="background:#6599FF;width:350px;">
<b>User input parameters and structure</b></div>
<ul>
<li>Interface similarity cutoff<br>
<font face="Courier">IS-score = $ISSCORE</font>
<br>
<li>Force field used for ΔΔG prediction<br>
<font face="Courier">$FF</font>
<li>Sequence [<a href=seq.fasta>download</a>]<br>
<font face="Courier">
>$CHAIN0<br>$SEQUENCE0<br>>$CHAIN1<br>$SEQUENCE1<br></font>
<br>
<li>View of 3D structure structure
<script type="text/javascript" src="$JSMOL0"></script>
<script type="text/javascript" src="$JSMOL1"></script>
<table>
<td align ="center">
complex structure [<a href=complex.pdb>download</a>]
<script type="text/javascript">
jmolInitialize("$JSMOL_HOME/");
jmolSetAppletColor("#000000");
jmolApplet(300,"load complex.pdb; set frank off; calculate structure rama; select all; color chain; spacefill off; wireframe off; cartoons; set ambient 40; set spin x 10; set spin y 10; spin off; $JSMOL_CMD");
</script>
</td>
<td align ="center">
interface structure [<a href=interface.pdb>download</a>]
<script type="text/javascript">
jmolInitialize("$JSMOL_HOME/");
jmolSetAppletColor("#000000");
jmolApplet(300,"load interface.pdb; select all; color chain; set ambient 40; set spin x 10; set spin y 10; spin off; $JSMOL_CMD");
</script>
</td>
</table>
</ul>
<div style="background:#6599FF;width:150px;">
<b>Results</b></div>
<ul>
<li>Binding affinity change upon mutations [<a href=result.txt>download</a>] [<a href=$HTTP_LINK/help.html#ddG>Explanation</a>]<br>
<font face="Courier">
DDG SSIPscore EvoEFscore mutations<br>
$RESULTS<br>
</font>
<br>
<li>Download structure models of all mutants [<a href=mutation_structures.tar.bz2>download</a>]
[<a href=$HTTP_LINK/help.html#forcefield>Explanation</a>]<br>
<br><br>
<li>Structure-based interface MSA by iAlign from NIL [<a href=structure_align.out>download</a>]
[<a href=$HTTP_LINK/help.html#structure_alignment>Explanation</a>]<br>
<font face="Courier">$ALIGN</font><br><br>
<li>Sequence-based interface MSA by PSI-BLAST from STRING [<a href=sequence_align.out>download</a>]
[<a href=$HTTP_LINK/help.html#sequence_alignment>Explanation</a>]<br>
<font face="Courier">$ALIGN2</font><br><br>
</ul>
<hr>
<b>Reference:</b>
<ul>$CITATION</ul>
[<a href="$HTTP_LINK">back to SSIPe server</a>]<br/>
</body></html>""")
# $HTTP_LINK - HTTP url to SSIPe web portal
# $JSMOL0 - first javascript for JSmol
# $JSMOL1 - second javascript for JSmol
# $JSMOL_HOME - JSmol javascript home
# $JSMOL_CMD - JSmol commands for highlighting interface residues
# $CITATION - citation for SSIPe paper
# $JOBID - webserver jobID
# $ALIGN - interface alignment
# $RESULTS - result list
# $ISSCORE - IS-score cutoff for interface simarity
# $FF - interface profile (and physics potential)
# $CHAIN0 - chain 0
# $SEQUENCE0 - sequence 0
# $CHAIN1 - chain 1
# $SEQUENCE1 - sequence 1
# template for JSMOL_CMD
jsmol_cmd_template = Template(
"select $RESI:$CHAIN; wireframe 75; spacefill 100; color $COLOR; select $RESI:$CHAIN and *.ca; label $RESN$CHAIN$RESI; color label magenta;"
)
# $RESI - residue index
# $CHAIN - chain ID
# $COLOR - residue color
# $RESN - residue amino acid type
#### read seq.fasta ####
chain_list = []
sequence_list = []
fasta_file = os.path.join(data_dir, "seq.fasta")
if os.path.isfile(fasta_file):
fp = open(fasta_file, 'rU')
txt = fp.read()
fp.close()
for block in txt.split('>'):
if block.strip():
block = block.splitlines()
chain_list.append(block[0])
sequence_list.append(''.join(block[1:]))
else:
header_list, sequence_list = pdb2seq(
os.path.join(data_dir, "complex.pdb"))
chain_list = [h.split(':')[-1] for h in header_list]
fp = open(fasta_file, 'w')
fp.write( ''.join(['>'+h+'\n'+s+'\n' \
for h,s in zip(header_list,sequence_list)]))
fp.close()
#### get all mutated residues ####
mutation_residue_list = []
for mutation_set in result_list:
for mutation in mutation_set.split()[1].rstrip(';').split(','):
resi = mutation[2:-1]
chain = mutation[1]
mutation_residue_list.append(chain + resi)
#### read structure_align.out ####
fp = open(os.path.join(data_dir, "structure_align.out"), 'rU')
txt = fp.read().replace('query', 'target')
fp.close()
align_txt = ''
jsmol_cmd = ''
for line in txt.splitlines():
align_txt += line + '<br>'
#don't label the mutated residues to make webpage faster
'''for line in txt.splitlines():
if line.startswith("chain_ID_A:"):
chain0=line[len("chain_ID_A:"):].strip()
elif line.startswith("chain_ID_B:"):
chain1=line[len("chain_ID_B:"):].strip()
elif line.startswith("residue_A:"):
txt="residue_A: "
for i in line[len("residue_A:"):].strip().split():
resi=inv_resi_dict[chain0][i] # residue index
txt+=' '+resi
if chain0+resi in mutation_residue_list:
resn=sequence_list[0][int(i)-1]
jsmol_cmd+=jsmol_cmd_template.substitute(dict(
RESI=resi,CHAIN=chain0,COLOR="blue",RESN=resn))
line=txt
elif line.startswith("residue_B:"):
txt="residue_B: "
for i in line[len("residue_B:"):].strip().split():
resi=inv_resi_dict[chain1][i] # residue index
txt+=' '+resi
if chain1+resi in mutation_residue_list:
resn=sequence_list[1][int(i)-1]
jsmol_cmd+=jsmol_cmd_template.substitute(dict(
RESI=resi,CHAIN=chain1,COLOR="yellow",RESN=resn))
line=txt
align_txt+=line+'<br>'
'''
#### read sequence_align.out ####
fp = open(os.path.join(data_dir, "sequence_align.out"), 'rU')
txt = fp.read().replace('query', 'target')
fp.close()
align_txt2 = ''
jsmol_cmd = ''
for line in txt.splitlines():
align_txt2 += line + '<br>'
#### write index.html ####
txt = html_template.substitute(
dict(
HTTP_LINK=http_link,
JSMOL0=javascript_list[0],
JSMOL1=javascript_list[1],
JSMOL_HOME=os.path.dirname(javascript_list[1]),
JSMOL_CMD=jsmol_cmd,
CITATION=citation,
JOBID=os.path.basename(data_dir),
ALIGN=align_txt,
ALIGN2=align_txt2,
RESULTS="<br>".join(result_list),
ISSCORE=isscore,
FF=force_field,
CHAIN0=chain_list[0],
SEQUENCE0="<br>".join(textwrap.wrap(sequence_list[0], 60)),
CHAIN1=chain_list[1],
SEQUENCE1="<br>".join(textwrap.wrap(sequence_list[1], 60)),
))
fp = open(os.path.join(data_dir, "index.html"), 'w')
fp.write(txt)
fp.close()
def get_final_score3(data_dir):
'''
4. run EvoEF, -> evoef_score.txt
5. get final score -> result.txt
'''
#### make temporary directory ####
tmp_dir = "/tmp/" + os.getenv("USER") + "/" + os.path.basename(data_dir)
if os.path.isdir(tmp_dir):
shutil.rmtree(tmp_dir)
os.makedirs(tmp_dir)
#### parse input files ####
isscore = "0.5"
force_field = "EVOEF"
isscore_file = os.path.join(data_dir, "isscore")
force_field_file = os.path.join(data_dir, "force_field")
pdb_file = os.path.join(data_dir, "complex.pdb")
seq_file = os.path.join(data_dir, "seq.fasta")
mutlist_file = os.path.join(data_dir, "mutList.txt")
align_file1 = os.path.join(data_dir, "structure_align.out")
align_file2 = os.path.join(data_dir, "sequence_align.out")
ssipscore_file = os.path.join(data_dir, "ssip_score.txt")
evoefscore_file = os.path.join(data_dir, "evoef_score.txt")
result_file = os.path.join(data_dir, "result.txt")
if os.path.isfile(isscore_file):
fp = open(isscore_file, 'rU')
isscore = fp.read().strip()
fp.close()
if os.path.isfile(force_field_file):
fp = open(force_field_file, 'rU')
force_field = fp.read().strip()
fp.close()
#### define temporary files ####
pdb_tmp = os.path.join(tmp_dir, "complex.pdb")
seq_tmp = os.path.join(tmp_dir, "seq.fasta")
align_tmp1 = os.path.join(tmp_dir, "structure_align.out")
align_tmp2 = os.path.join(tmp_dir, "sequence_align.out")
mutlist_tmp = os.path.join(tmp_dir, "mutList.txt")
ssipscore_tmp = os.path.join(tmp_dir, "ssip_score.txt")
evoefscore_tmp = os.path.join(tmp_dir, "evoef_score.txt")
#### renumber residue index and output the files to temporary folder ####
#resi_dict,inv_resi_dict=reindex_complex(mutlist_file,pdb_file,mutlist_tmp,pdb_tmp)
shutil.copy(mutlist_file, mutlist_tmp)
shutil.copy(pdb_file, pdb_tmp)
#### get evoef score ####
sys.stdout.write("step 4: get_evoef_score\n")
if force_field == "EVOEF":
if os.path.isfile(evoefscore_file):
shutil.copy(evoefscore_file, evoefscore_tmp)
else:
#shutil.copy(pdb_file,pdb_tmp)
cmd = ' '.join([
"cd", tmp_dir, ';', run_evoef, pdb_tmp, mutlist_tmp,
evoefscore_tmp
])
os.system(cmd)
shutil.copy(evoefscore_tmp, evoefscore_file)
#### get final score ####
sys.stdout.write("step 5: get_final_score\n")
fp = open(mutlist_file, 'rU')
mutation_list = fp.read().strip().splitlines()
fp.close()
fp = open(evoefscore_tmp, 'rU')
evoefscore_list = [float(f) for f in fp.read().splitlines()]
fp.close()
finalscore_list = evoefscore_list
result_list = [
"%-7.3f %-10.3f %s" % (f, e, m)
for f, e, m in zip(finalscore_list, evoefscore_list, mutation_list)
]
fp = open(result_file, 'w')
fp.write('DDG EvoEFscore mutations\n')
fp.write('\n'.join(result_list) + '\n')
fp.close()
#### copy mutant PDB structure if available ####
for mutation in mutation_list:
mutant_file = os.path.join(
data_dir,
"complex_" + mutation.rstrip(';').replace(',', '_') + ".pdb")
mutant_tmp = os.path.join(
tmp_dir,
"complex_" + mutation.rstrip(';').replace(',', '_') + ".pdb")
if os.path.isfile(mutant_tmp):
shutil.copy(mutant_tmp, mutant_file)
cmd = ' '.join([
"cd", tmp_dir, ";",
"tar -jcvf mutation_structures.tar.bz2 complex_*.pdb"
])
os.system(cmd)
shutil.copy(os.path.join(tmp_dir, "mutation_structures.tar.bz2"),
os.path.join(data_dir, "mutation_structures.tar.bz2"))
#get chain list
header_list, sequence_list = pdb2seq(pdb_file)
chain_list = [h.split(':')[-1] for h in header_list]
#### extract interface PDB file ####
cmd = ' '.join([
extint, "-s", pdb_file, "-r", chain_list[0], "-l", chain_list[1], "-c",
os.path.join(data_dir, "contact.list"), "-i",
os.path.join(data_dir, "interface.pdb")
])
os.system(cmd)
#### make html output ####
sys.stdout.write("step 6: index.html\n")
#make_webpage3(inv_resi_dict,data_dir,isscore,force_field,result_list)
make_webpage3(data_dir, isscore, force_field, result_list)
#### clean up temporary directory ####
shutil.rmtree(tmp_dir)
return