Ссылка на практикум

Сутью задания является ознакомиться с программой ZDOCK и сделать предсказание о связывании фрагмента антитела (VHH domain) c панкреатической альфа-амилазой.

Перед началом работы укажем путь к zdock:

In [1]:
%%bash
export LD_LIBRARY_PATH=${LD_LIBRARY_PATH}:/home/preps/golovin/progs/lib
export PATH=${PATH}:/home/preps/golovin/progs/bin

Скопируем в рабочую директорию необходимые файлы:

In [2]:
%%bash
wget http://kodomo.cmm.msu.ru/~golovin/zdock/amylase.pdb
wget http://kodomo.cmm.msu.ru/~golovin/zdock/camelid.pdb
wget http://kodomo.cmm.msu.ru/~golovin/zdock/uniCHARMM
--2016-05-12 15:48:52--  http://kodomo.cmm.msu.ru/~golovin/zdock/amylase.pdb
Resolving kodomo.cmm.msu.ru... 93.180.63.127
Connecting to kodomo.cmm.msu.ru|93.180.63.127|:80... connected.
HTTP request sent, awaiting response... 200 OK
Length: 387504 (378K) [chemical/x-pdb]
Saving to: `amylase.pdb'

     0K .......... .......... .......... .......... .......... 13%  108M 0s
    50K .......... .......... .......... .......... .......... 26%  294M 0s
   100K .......... .......... .......... .......... .......... 39%  297M 0s
   150K .......... .......... .......... .......... .......... 52%  296M 0s
   200K .......... .......... .......... .......... .......... 66%  417M 0s
   250K .......... .......... .......... .......... .......... 79%  363M 0s
   300K .......... .......... .......... .......... .......... 92%  401M 0s
   350K .......... .......... ........                        100%  336M=0.001s

2016-05-12 15:48:52 (263 MB/s) - `amylase.pdb' saved [387504/387504]

--2016-05-12 15:48:52--  http://kodomo.cmm.msu.ru/~golovin/zdock/camelid.pdb
Resolving kodomo.cmm.msu.ru... 93.180.63.127
Connecting to kodomo.cmm.msu.ru|93.180.63.127|:80... connected.
HTTP request sent, awaiting response... 200 OK
Length: 73224 (72K) [chemical/x-pdb]
Saving to: `camelid.pdb'

     0K .......... .......... .......... .......... .......... 69%  198M 0s
    50K .......... .......... .                               100%  402M=0s

2016-05-12 15:48:52 (234 MB/s) - `camelid.pdb' saved [73224/73224]

--2016-05-12 15:48:52--  http://kodomo.cmm.msu.ru/~golovin/zdock/uniCHARMM
Resolving kodomo.cmm.msu.ru... 93.180.63.127
Connecting to kodomo.cmm.msu.ru|93.180.63.127|:80... connected.
HTTP request sent, awaiting response... 200 OK
Length: 17376 (17K)
Saving to: `uniCHARMM'

     0K .......... ......                                     100%  207M=0s

2016-05-12 15:48:52 (207 MB/s) - `uniCHARMM' saved [17376/17376]


Добавим водороды к обоим pdb исполльзуя pdb2gmx (выбирая силовое поле 13: GROMOS96 53a6 и модель воды 1: SPC):

In [3]:
%%bash
pdb2gmx -f amylase.pdb -o amylase_h.pdb -p -ignh
pdb2gmx -f camelid.pdb -o camelid_h.pdb -p -ignh
Process is terminated.

С помощью утилиты mark_sur (Mark the surface residues of a PDB file) проведём препроцессинг файлов pdb:

In []:
%%bash
mark_sur amylase_h.pdb amylase_m.pdb
mark_sur camelid_h.pdb camelid_m.pdb

Для успешной работы zrank и zdock из pdb файлов надо удалить строчки MODEL и TER:

In [8]:
%%bash
sed -i '/MODEL        1/d' amylase_m.pdb
sed -i '/TER/d' amylase_m.pdb
sed -i '/MODEL        1/d' camelid_m.pdb
sed -i '/TER/d' camelid_m.pdb

Запустим процесс докинга:

In [9]:
%%bash
zdock -R amylase_m.pdb -L camelid_m.pdb
bash: line 1: zdock: command not found

Проведём предварительный анализ результатов докинга с помощью утилиты zrank:

In []:
%%bash
sed -i '-2.617994       0.419640        2.974122/d' zdock.out
sed '/camelid_m.pdb   27.065  -10.816 -16.094/a \
' zdock.out
In [10]:
%%bash
zrank zdock.out.cp 1 2000
bash: line 1: zrank: command not found

In [12]:
%%bash
sort -n -k2 zdock.out.zr.out | head
1560	-28.661
1223	-27.5357
595	-25.5514
1409	-22.3979
1935	-21.1778
916	-17.5643
822	-14.7274
655	-13.8186
1642	-11.6282
1077	-10.8227

sort: write failed: standard output: Broken pipe
sort: write error

Визуально сравним результаты с известной структурой 1kxt:

In [13]:
%%bash
wget http://files.rcsb.org/download/1KXT.pdb
--2016-05-12 17:14:59--  http://files.rcsb.org/download/1KXT.pdb
Resolving files.rcsb.org... 132.249.213.77
Connecting to files.rcsb.org|132.249.213.77|:80... connected.
HTTP request sent, awaiting response... 200 OK
Length: unspecified [application/octet-stream]
Saving to: `1KXT.pdb'

     0K .......... .......... .......... .......... .......... 80.4K
    50K .......... .......... .......... .......... .......... 80.4K
   100K .......... .......... .......... .......... .......... 80.4K
   150K .......... .......... .......... .......... .......... 80.4K
   200K .......... .......... .......... .......... ..........  120K
   250K .......... .......... .......... .......... ..........  102K
   300K .......... .......... .......... .......... .......... 80.5K
   350K .......... .......... .......... .......... ..........  121K
   400K .......... .......... .......... .......... .......... 91.6K
   450K .......... .......... .......... .......... ..........  121K
   500K .......... .......... .......... .......... ..........  102K
   550K .......... .......... .......... .......... ..........  121K
   600K .......... .......... .......... .......... .......... 80.5K
   650K .......... .......... .......... .......... ..........  147K
   700K .......... .......... .......... .......... ..........  102K
   750K .......... .......... .......... .......... ..........  121K
   800K .......... .......... .......... .......... ..........  120K
   850K .......... .......... .......... .......... ..........  121K
   900K .......... .......... .......... .......... ..........  121K
   950K .......... .......... .......... .......... ..........  110K
  1000K .......... .......... .......... .......... ..........  111K
  1050K .......... .......... .......... .......... ..........  121K
  1100K .......... .......... .......... .......... ..........  121K
  1150K .......... .......... .......... .......... ..........  121K
  1200K .......... .......... .......... .......... ..........  121K
  1250K .......... .......... .......... .......... ..........  132K
  1300K .......... .......... .......... .......... ..........  111K
  1350K .......... .......... .                                 104K=13s

2016-05-12 17:15:12 (106 KB/s) - `1KXT.pdb' saved [1404459]


In []: