时间不充分，简单记录下自己实践过程中的做法:

1. 首先，非标准残基都需要转换成.params文件，使用 <path-to-Rosetta>/main/source/scripts/python/public/molfile_to_params.py -n TPP TPP.mol2 --chain=F --clobber 转换，此命令会产生TPP_0001.pdb和TPP.params两个文件；

2. 其次，如果配体需要进行构象搜索，可以使用obabel，这个免费且简单，见博客http://www.cnblogs.com/wq242424/p/8231600.html，需要做限制性构象搜索的话，就比较难了，我用的是schrodinger的conformational search里的高级搜索；

3. 如果经过上一步产生了ligand_conformers.sdf，就需要为 <path-to-Rosetta>/main/source/scripts/python/public/molfile_to_params.py -n GAD -p GAD --chain=X --center=-31,-35.5,8 --clobber --conformers-in-one-file GAD_confs.sdf 命令多加一个参数 --conformers-in-one-file GAD_confs.sdf ，这个参数会在产生的.params文件末尾加一句 PDB_ROTAMERS GAD_conformers.pdb 来表明你的多重构象的文件，此命令会产生GAD.pdb，GAD.params和GAD_conformers.pdb三个文件，其中GAD.pdb是以conformers中第一个构象为结构；

4. 多底物对接的问题，经过查阅手册和论坛，得出的结论是通过控制需要dock的链("X/Y/F/。。。")来指定需要对接的小分子，比如我要对接TPP和GAD，就需要在single movers后面及前面LIGAND_AREAS和INTERFACE_BUILDERS那里指定分别对“F”和“X”链进行dock，并在MOVERS处指定两底物分子分别对应的操作，options不必特意根据双底物改变，下面给出了我做的两个XML文件的示例；

5. StartFrom,Transform,Translate和Rotate的差别和比较。StartFrom是在底物不在蛋白口袋内部，需要程序先将底物以Coordinates为基准放到口袋中的程序；Transform是使用蒙特卡洛的方法，对对接过程的底物和蛋白小分子随机取样的过程；Translate和Rotate则是对处于口袋中的小分子进行平移旋转的操作。底物在蛋白口袋中时，就可以不使用StartFrom；使用Transform时，则需要指定GRID。

6. 至于下面的high_resolution_dock XML文件，用途是在你已经知道你的底物的位置的情况下，对底物及周边残基进行高分辨率的对接，与其说对接，可能说packing和minimizing更恰当，因为它是对周围的残基优化的同时变换底物的构象，以求找到最优结果。

分享一下自己的两个xml文件及对应的flags：

low_resolution_dock+high_resolution_dock

This protocol will simply do low-resolution followed by high-resolution docking.

It will also report the binding energy (ddg) and buried-surface area (sasa) in the score file.

<ROSETTASCRIPTS>

	<SCOREFXNS>

		<ligand_soft_rep weights="ligand_soft_rep">

		</ligand_soft_rep>

		<hard_rep weights="ligand">

		</hard_rep>

	</SCOREFXNS>

	<LIGAND_AREAS>

		<docking_sidechain_X chain="X" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true" minimize_ligand="10"/>

		<final_sidechain_X chain="X" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true"/>

		<final_backbone_X chain="X" cutoff="7.0" add_nbr_radius="false" all_atom_mode="true" Calpha_restraints="0.3"/>

	</LIGAND_AREAS>

	<INTERFACE_BUILDERS>

		<side_chain_for_docking ligand_areas="docking_sidechain_X"/>

		<side_chain_for_final ligand_areas="final_sidechain_X"/>

		<backbone ligand_areas="final_backbone_X" extension_window="3"/>

	</INTERFACE_BUILDERS>

	<MOVEMAP_BUILDERS>

		<docking sc_interface="side_chain_for_docking" minimize_water="true"/>

		<final sc_interface="side_chain_for_final" bb_interface="backbone" minimize_water="true"/>

	</MOVEMAP_BUILDERS>

	<MOVERS>

	single movers

		<StartFrom name="start_from_X" chain="X">

			<Coordinates x="-31" y="-35.5" z="8"/>

		</StartFrom>

		<CompoundTranslate name="compound_translate" randomize_order="false" allow_overlap="false">

			<Translate chain="X" distribution="uniform" angstroms="2.0" cycles="50"/>

		</CompoundTranslate>

		<Rotate name="rotate_X" chain="X" distribution="uniform" degrees="360" cycles="500"/>

		<SlideTogether name="slide_together" chains="X"/>

		<HighResDocker name="high_res_docker" cycles="6" repack_every_Nth="3" scorefxn="ligand_soft_rep" movemap_builder="docking"/>

		<FinalMinimizer name="final" scorefxn="hard_rep" movemap_builder="final"/>

		<InterfaceScoreCalculator name="add_scores" chains="X" scorefxn="hard_rep"/>

	compound movers

		<ParsedProtocol name="low_res_dock">

			<Add mover_name="start_from_X"/>

			<Add mover_name="compound_translate"/>

			<Add mover_name="rotate_X"/>

			<Add mover_name="slide_together"/>

		</ParsedProtocol>

		<ParsedProtocol name="high_res_dock">

			<Add mover_name="high_res_docker"/>

			<Add mover_name="final"/>

		</ParsedProtocol>

	</MOVERS>

	<PROTOCOLS>

		<Add mover_name="low_res_dock"/>

		<Add mover_name="high_res_dock"/>

		<Add mover_name="add_scores"/>

	</PROTOCOLS>

</ROSETTASCRIPTS>

对应的flag options文件：

-in:file:s inputs_GAD/GALS_TPP_GAD.pdb

-in:file:extra_res_fa inputs_GAD/TPP.params inputs_GAD/GAD.params

-packing

	-ex1

	-ex2aro

	-ex2

	-no_optH false

	-flip_HNQ true

	-ignore_ligand_chi true

-parser

	-protocol inputs_GAD/ligand_dock.xml

-out

	-path:all outputs_GAD

	-nstruct 1000

	-overwrite

high_resolution_dock_only

This protocol will simply do high-resolution docking.

It will also report the binding energy (ddg) and buried-surface area (sasa) in the score file.

<ROSETTASCRIPTS>

	<SCOREFXNS>

		<ligand_soft_rep weights="ligand_soft_rep">

		</ligand_soft_rep>

		<hard_rep weights="ligand">

		</hard_rep>

	</SCOREFXNS>

	<LIGAND_AREAS>

		<docking_sidechain_X chain="X" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true" minimize_ligand="10"/>

		<final_sidechain_X chain="X" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true"/>

		<final_backbone_X chain="X" cutoff="7.0" add_nbr_radius="false" all_atom_mode="true" Calpha_restraints="0.3"/>

	</LIGAND_AREAS>

	<INTERFACE_BUILDERS>

		<side_chain_for_docking ligand_areas="docking_sidechain_X"/>

		<side_chain_for_final ligand_areas="final_sidechain_X"/>

		<backbone ligand_areas="final_backbone_X" extension_window="3"/>

	</INTERFACE_BUILDERS>

	<MOVEMAP_BUILDERS>

		<docking sc_interface="side_chain_for_docking" minimize_water="true"/>

		<final sc_interface="side_chain_for_final" bb_interface="backbone" minimize_water="true"/>

	</MOVEMAP_BUILDERS>

	<SCORINGGRIDS ligand_chain="X" width="15">

		<classic grid_type="ClassicGrid" weight="1.0"/>

	</SCORINGGRIDS>

	<MOVERS>

		<Transform name="transform" chain="X"box_size="7.0" move_distance="0.2" angle="20" cycles="500" repeats="1" temperature="5"/>

		<HighResDocker name="high_res_docker" cycles="6" repack_every_Nth="3" scorefxn="ligand_soft_rep" movemap_builder="docking"/>

		<FinalMinimizer name="final" scorefxn="hard_rep" movemap_builder="final"/>

		<InterfaceScoreCalculator name="add_scores" chains="X" scorefxn="hard_rep"/>

	</MOVERS>

	<PROTOCOLS>

		<Add mover_name="transform"/>

		<Add mover_name="high_res_docker"/>

		<Add mover_name="final"/>

		<Add mover_name="add_scores"/>

	</PROTOCOLS>

</ROSETTASCRIPTS>

对应的flag_options文件：

-in:file:s inputs_IMA/GALS_IMA.pdb

-in:file:extra_res_fa inputs_IMA/IMA.params

-packing

	-ex1

	-ex2aro

	-ex2

	-no_optH false

	-flip_HNQ true

	-ignore_ligand_chi true

-parser

	-protocol inputs_IMA/ligand_dock.xml

-out

	-path:all outputs_IMA

	-nstruct 1000

	-overwrite

多底物对接（两个小分子的链分别对应“X”和“F”）

1. 手动指定两个小分子（“X”，“F”）的位置（使用StartFrom mover指定，对应的Coordinates）
This protocol will simply do low-resolution followed by high-resolution docking.

It will also report the binding energy (ddg) and buried-surface area (sasa) in the score file.

<ROSETTASCRIPTS>

	<SCOREFXNS>

		<ligand_soft_rep weights="ligand_soft_rep">

		</ligand_soft_rep>

		<hard_rep weights="ligand">

		</hard_rep>

	</SCOREFXNS>

	<LIGAND_AREAS>

		<docking_sidechain_X chain="X" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true" minimize_ligand="10"/>

		<final_sidechain_X chain="X" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true"/>

		<final_backbone_X chain="X" cutoff="7.0" add_nbr_radius="false" all_atom_mode="true" Calpha_restraints="0.3"/>

		<docking_sidechain_F chain="F" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true" minimize_ligand="10"/>

		<final_sidechain_F chain="F" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true"/>

		<final_backbone_F chain="F" cutoff="7.0" add_nbr_radius="false" all_atom_mode="true" Calpha_restraints="0.3"/>

	</LIGAND_AREAS>

	<INTERFACE_BUILDERS>

		<side_chain_for_docking ligand_areas="docking_sidechain_X,docking_sidechain_F"/>

		<side_chain_for_final ligand_areas="final_sidechain_X,final_sidechain_F"/>

		<backbone ligand_areas="final_backbone_X,final_backbone_F" extension_window="3"/>

	</INTERFACE_BUILDERS>

	<MOVEMAP_BUILDERS>

		<docking sc_interface="side_chain_for_docking" minimize_water="true"/>

		<final sc_interface="side_chain_for_final" bb_interface="backbone" minimize_water="true"/>

	</MOVEMAP_BUILDERS>

	<MOVERS>

	single movers_X

		<StartFrom name="start_from_X" chain="X">

			<Coordinates x="-31" y="-35.5" z="8"/>

		</StartFrom>

		<StartFrom name="start_from_F" chain="F">

			<Coordinates x="-27.26" y="-34.56" z="4.87"/>

		</StartFrom>

		<CompoundTranslate name="compound_translate" randomize_order="false" allow_overlap="false">

			<Translate chain="X" distribution="uniform" angstroms="2.0" cycles="50"/>

			<Translate chain="F" distribution="uniform" angstroms="2.0" cycles="50"/>

		</CompoundTranslate>

		<Rotate name="rotate_X" chain="X" distribution="uniform" degrees="360" cycles="500"/>

		<Rotate name="rotate_F" chain="F" distribution="uniform" degrees="360" cycles="500"/>

		<SlideTogether name="slide_together" chains="X,F"/>

		<HighResDocker name="high_res_docker" cycles="6" repack_every_Nth="3" scorefxn="ligand_soft_rep" movemap_builder="docking"/>

		<FinalMinimizer name="final" scorefxn="hard_rep" movemap_builder="final"/>

		<InterfaceScoreCalculator name="add_scores" chains="X,F" scorefxn="hard_rep"/>

	compound movers

		<ParsedProtocol name="low_res_dock">

			<Add mover_name="start_from_X"/>

			<Add mover_name="start_from_F"/>

			<Add mover_name="compound_translate"/>

			<Add mover_name="rotate_X"/>

			<Add mover_name="rotate_F"/>

			<Add mover_name="slide_together"/>

		</ParsedProtocol>

		<ParsedProtocol name="high_res_dock">

			<Add mover_name="high_res_docker"/>

			<Add mover_name="final"/>

		</ParsedProtocol>

	</MOVERS>

	<PROTOCOLS>

		<Add mover_name="low_res_dock"/>

		<Add mover_name="high_res_dock"/>

		<Add mover_name="add_scores"/>

	</PROTOCOLS>

</ROSETTASCRIPTS> 
2. 其中一个小分子（“F”）位置已知，另一个小分子（“X”）的位置需要指定（首先需使用SCORINGGRIDS为已知位置的小分子指定盒子，然后使用Transform指定其动作模式）
This protocol will simply do low-resolution followed by high-resolution docking.

It will also report the binding energy (ddg) and buried-surface area (sasa) in the score file.

<ROSETTASCRIPTS>

	<SCOREFXNS>

		<ligand_soft_rep weights="ligand_soft_rep">

		</ligand_soft_rep>

		<hard_rep weights="ligand">

		</hard_rep>

	</SCOREFXNS>

	<LIGAND_AREAS>

		<docking_sidechain_X chain="X" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true" minimize_ligand="10"/>

		<final_sidechain_X chain="X" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true"/>

		<final_backbone_X chain="X" cutoff="7.0" add_nbr_radius="false" all_atom_mode="true" Calpha_restraints="0.3"/>

		<docking_sidechain_F chain="F" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true" minimize_ligand="10"/>

		<final_sidechain_F chain="F" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true"/>

		<final_backbone_F chain="F" cutoff="7.0" add_nbr_radius="false" all_atom_mode="true" Calpha_restraints="0.3"/>

	</LIGAND_AREAS>

	<INTERFACE_BUILDERS>

		<side_chain_for_docking ligand_areas="docking_sidechain_X,docking_sidechain_F"/>

		<side_chain_for_final ligand_areas="final_sidechain_X,final_sidechain_F"/>

		<backbone ligand_areas="final_backbone_X,final_backbone_F" extension_window="3"/>

	</INTERFACE_BUILDERS>

	<MOVEMAP_BUILDERS>

		<docking sc_interface="side_chain_for_docking" minimize_water="true"/>

		<final sc_interface="side_chain_for_final" bb_interface="backbone" minimize_water="true"/>

	</MOVEMAP_BUILDERS>

	<SCORINGGRIDS ligand_chain="F" width="15">

		<classic grid_type="ClassicGrid" weight="1.0"/>

	</SCORINGGRIDS>

	<MOVERS>

	single movers_X

		<StartFrom name="start_from_X" chain="X">

			<Coordinates x="-31" y="-35.5" z="8"/>

		</StartFrom>

		<Transform name="transform_F" chain="F" box_size="7.0" move_distance="0.2" angle="20" cycles="500" repeats="1" temperature="5"/>

		<CompoundTranslate name="compound_translate" randomize_order="false" allow_overlap="false">

			<Translate chain="X" distribution="uniform" angstroms="2.0" cycles="50"/>

			<Translate chain="F" distribution="uniform" angstroms="2.0" cycles="50"/>

		</CompoundTranslate>

		<Rotate name="rotate_X" chain="X" distribution="uniform" degrees="360" cycles="500"/>

		<Rotate name="rotate_F" chain="F" distribution="uniform" degrees="360" cycles="500"/>

		<SlideTogether name="slide_together" chains="X,F"/>

		<HighResDocker name="high_res_docker" cycles="6" repack_every_Nth="3" scorefxn="ligand_soft_rep" movemap_builder="docking"/>

		<FinalMinimizer name="final" scorefxn="hard_rep" movemap_builder="final"/>

		<InterfaceScoreCalculator name="add_scores" chains="X,F" scorefxn="hard_rep"/>

	compound movers

		<ParsedProtocol name="low_res_dock">

			<Add mover_name="start_from_X"/>

			<Add mover_name="transform_F"/>

			<Add mover_name="compound_translate"/>

			<Add mover_name="rotate_X"/>

			<Add mover_name="rotate_F"/>

			<Add mover_name="slide_together"/>

		</ParsedProtocol>

		<ParsedProtocol name="high_res_dock">

			<Add mover_name="high_res_docker"/>

			<Add mover_name="final"/>

		</ParsedProtocol>

	</MOVERS>

	<PROTOCOLS>

		<Add mover_name="low_res_dock"/>

		<Add mover_name="high_res_dock"/>

		<Add mover_name="add_scores"/>

	</PROTOCOLS>

</ROSETTASCRIPTS>

　　

ROSETTA使用技巧随笔--RosettaLigand Docking的更多相关文章

  1. ROSETTA使用技巧随笔--蛋白蛋白对接

    先写简略版,以后再详细写. 1. 对输入结构进行预处理(refine) $> relax.default.linuxgccrelease -in:file:s input_files/from_ ...

  2. ROSETTA使用技巧随笔--relax使用

    Purpose: 主要说目的,relax的作用就是对一个给定的蛋白进行构象搜索,寻找与WT相似并能量低于WT的结构,既包含packer又包含minimizer.主要的应用在对一个结构构象进行取样,获得 ...

  3. ROSETTA使用技巧随笔--PyMOL实时观测ROSETTA模拟过程中的结构变化

    没有梦想的人,就是一只咸鱼,像我,就有一个梦想,就是让蛋白模拟过程变成动画,动起来! 虽然MD中有很多方法可以方模拟过程像动画一样播放出来,但是我一直想在ROSETTA中也找一个这样的功能,这不,我发 ...

  4. ROSETTA使用技巧随笔--控制Log输出等级

    一般运行ROSETTA,屏幕上的Log很多,而且很复杂,让我们看着眼晕,现在我们可以通过控制Log等级来控制屏幕上输出的东西.  Integer Level 0 Fatal 100 Error 200 ...

  5. ROSETTA使用技巧随笔--Full Atom Representation和Centroid Representation

    Full Atom Representation vs Centroid Representation Full Atom Representation即全原子标识,氨基酸残基的所有相关原子,均原封不 ...

  6. ROSETTA使用技巧随笔--score.sc处理

    对score.sc的便利操作: $ sort -n -k2 example_score_file.sc 此命令会以score文件的第二列进行排序(sort -n -k2,-n表示对数值型数据排序,可用 ...

  7. RF常用技巧随笔

    合并xml输出文件: pybot --outputdir d:\test --log log1.html --report report1.html --output output1.xml -T d ...

  8. angular小技巧随笔

    1. 重新刷新页面 同页面切换状态: $state.go('tab.index', {inviteId:inviteId}); self.location.reload();

  9. JavaScript小技巧随笔

    1. 在用||做条件判断时,如果情况较多,我们可以考虑是否能够用Array.includes()方法代替 var conditionArray = [ test1, test2, test3 ]; i ...

随机推荐

  1. 在ASP.NET Core中实现自定义验证特性(Custom Validation Attribute)

    这是我们在实际ASP.NET Core项目中用到的,验证用户名中是否包含空格. 开始是这么实现的(继承ValidationAttribute,重写IsValid方法): public class No ...

  2. c++基本函数

    std::abs 求绝对值函数 double abs (double x); float abs (float x); long double abs (long double x); std::sw ...

  3. linux shutdown命令以及参数详解

    在说shutdown命令之前 先说一下sync命令: sync:将内存中尚未写入硬盘的数据写入硬盘 因为linux为了保证数据读写速度,把常用的数据放在内存中,不会立即写入硬盘,如果有不当关机,这些数 ...

  4. ubuntu下能ping通ssh不通的解决思路

    1.首先看看是否能ping通,如果ping不通可能就要考虑网线.路由等问题了: 2.看防火墙是否关闭,sshd是否开启 3.ssh -v 服务器的ip号,根据提示寻找可能的问题: 我的问题在这一步之后 ...

  5. Vue2 dist 目录下各个文件的区别

    vue2 经过 2.2 版本升级后, 文件变成了 8 个: vue.common.js vue.esm.js vue.js vue.min.js vue.runtime.common.js vue.r ...

  6. char是所有类型中最短的 char多为8位，

    https://en.wikipedia.org/wiki/C_data_typesIn practice, char is usually eight bits in size and short ...

  7. day0315 迭代器

    一. 迭代器 1.什么是可迭代器? 除了数字和布尔值之外,其他数据类型都是可迭代对象.(字符串,列表,元组,字典,集合) 2.可迭代协议 2.1 可以被迭代要满足的要求就叫可迭代协议,可迭代的定义非常 ...

  8. Python3+Selenium环境配置

    一.所需工具 1.Python3.6安装包 2.Selenium安装包(selenium-server-standalone-3.8),如果是Python3的话可以不用下载selenium压缩包,Py ...

  9. RENAME方法进行分区改造

    1.新建零时表 set time on timing on create table RPTUSER.RPT_TMP_10086BDL_bak ( HANDLEDATE DATE, TEL_CALLI ...

  10. Feature如何解决参数数量不匹配

    问题描述: Feature 写了两个参数,匹配到Steps.Java,  文件只写了两个参数,但是两个参数都加了$ 符号. 而$ 又是结束的意思. 1一:Feature  用例