Rosetta基础3：ligand docking

1. 对蛋白预处理：

[user@localhost protein]$ /usr/local/python-2.7.16/bin/python2 $ROSETTA/tools/protein_tools/scripts/clean_pdb.py D14_protein.pdb A
Found existing PDB file at D14_protein.pdb
D14_protein A   *** --- --- MOD --- OK
>D14_protein_A
MTQVVLGSGVIGLS....AQKGYKVHVVP.....EDTYAQWAGAA.....WNPEAGPRQSA

2. 对配体预处理参考Rosetta基础2-preparing ligand
3. 分子对接
   对接的文件夹中包含
   配体： UNK_conformers.pdb、UNK.params、 UNK.pdb
   蛋白：D14_protein_A.pdb
   对接参数文件：dock.xml和options

[user@localhost docking]$ ll
total 292
-rw-rw-r-- 1 user user 224455 Aug  4 02:57 D14_protein_A.pdb
-rw-r--r-- 1 user user   1937 Aug  4 03:00 dock.xml
-rw-r--r-- 1 user user   1004 Aug  4 03:00 options
-rw-rw-r-- 1 user user  56376 Aug  4 02:58 UNK_conformers.pdb
-rw-rw-r-- 1 user user   3233 Aug  4 02:58 UNK.params
-rw-rw-r-- 1 user user   1944 Aug  4 02:58 UNK.pdb

# 生成蛋白配体复合物
[user@localhost docking]$ cat D14_protein_A.pdb UNK.pdb > D14_protein_A_UNK.pdb
[user@localhost docking]$ ll
total 516
-rw-rw-r-- 1 user user 224455 Aug  4 02:57 D14_protein_A.pdb
-rw-rw-r-- 1 user user 226399 Aug  4 03:00 D14_protein_A_UNK.pdb
-rw-r--r-- 1 user user   1937 Aug  4 03:00 dock.xml
-rw-r--r-- 1 user user   1004 Aug  4 03:00 options
-rw-rw-r-- 1 user user  56376 Aug  4 02:58 UNK_conformers.pdb
-rw-rw-r-- 1 user user   3233 Aug  4 02:58 UNK.params
-rw-rw-r-- 1 user user   1944 Aug  4 02:58 UNK.pdb

#运行对接命令：
[user@localhost docking]$ $ROSETTA/main/source/bin/rosetta_scripts.linuxgccrelease @options
core.init: Checking for fconfig files in pwd and ./rosetta/flags
core.init: Rosetta version: rosetta.source.release-215 r215 2019.12+release.46f270e 46f270eaa6df591e0db5e65cdd09b31ec37b7d41 https://www.rosettacommons.org 2019-03-23T16:00:28.850418
core.init: command: /home/user/software/rosetta_src_2019.12.60667_bundle/main/source/bin/rosetta_scripts.linuxgccrelease @options
core.init: 'RNG device' seed mode, using '/dev/urandom', seed=-1122630614 seed_offset=0 real_seed=-1122630614
core.init.random: RandomGenerator:init: Normal mode, seed=-1122630614 RG_type=mt19937
core.init: found database environment variable ROSETTA3_DB: /home/user/software/rosetta_src_2019.12.60667_bundle/main/database
protocols.jd2.PDBJobInputter: Instantiate PDBJobInputter
.........
protocols.qsar.scoring_grid.GridManager: No conformation matching hash: f6fa989691fb0447be2f0dd10ce75ee4ccf31a23 Updating grid and adding it to the cache
protocols.rosetta_scripts.ParsedProtocol: setting status to success
protocols.jd2.JobDistributor: D14_protein_A_UNK_0005 reported success in 7 seconds
protocols.jd2.JobDistributor: no more batches to process...
protocols.jd2.JobDistributor: 5 jobs considered, 5 jobs attempted in 49 seconds

运行结束后

[user@localhost docking]$ ll
total 2964
-rw-rw-r-- 1 user user 224455 Aug  4 02:57 D14_protein_A.pdb
-rw-rw-r-- 1 user user 497138 Aug  4 03:03 D14_protein_A_UNK_0001.pdb
-rw-rw-r-- 1 user user 497051 Aug  4 03:04 D14_protein_A_UNK_0002.pdb
-rw-rw-r-- 1 user user 496960 Aug  4 03:04 D14_protein_A_UNK_0003.pdb
-rw-rw-r-- 1 user user 497139 Aug  4 03:04 D14_protein_A_UNK_0004.pdb
-rw-rw-r-- 1 user user 496977 Aug  4 03:04 D14_protein_A_UNK_0005.pdb
-rw-rw-r-- 1 user user 226399 Aug  4 03:00 D14_protein_A_UNK.pdb
-rw-r--r-- 1 user user   1908 Aug  4 03:02 dock.xml
-rw-r--r-- 1 user user   1015 Aug  4 03:01 options
-rw-rw-r-- 1 user user   5219 Aug  4 03:04 score.sc
-rw-rw-r-- 1 user user  56376 Aug  4 02:58 UNK_conformers.pdb
-rw-rw-r-- 1 user user   3233 Aug  4 02:58 UNK.params
-rw-rw-r-- 1 user user   1944 Aug  4 02:58 UNK.pdb

做完分子对接的例子，有两个问题：

1. 写的这篇总结中dock.xml里没有native="crystal_complex.pdb"这个选项，能正常运行；但是Ligand-docking-tutorial教程中dock.xml中有 native=“crystal_complex.pdb”，这个是为啥？既然有晶体结构为什么还要做对接呢？没有晶体结构的蛋白-配体怎么办？

2. 分子对接时，小分子和蛋白的结合区域是被指定(DS或者Autodock)，只是配体构像变化导致与蛋白结合位点产生差异。
   没明白Rosetta对接时怎么指定结合区域，dock.xml还要在研究研究，后面会更新这篇总结

欢迎各位小伙伴给我留言，写出自己的解析，谢谢
参考链接 Rosetta – Ligand-docking-tutorial