Back

非常有用的蛋白质科学工具与项目

翻译自,github:(2015版)

蛋白配体对接与评价

AutoDock 4.2

License:free, open-source (GNU GPL)

一个使用相对廉价的"hybrid"力场的分子对接与得分工具,该力场为半经验的方法(molecular mechanics as well as empirical terms).其预测的绝对结合自由能相较于更大的计算量项目可能精确度较低,但这种半经验方法对于相对得分(ranking)可能更加合适。

虽然AutoDock这种半经验力场被AutoDock Vina这个完整的基于知识的,统计得分函数的软件所替代。同时AutoDock Vina具有更精确和更快的速度。但是AutoDock 4.2 提供了更加详细的输出描述可能对某些应用具有其独有的优势。

网址:http://autodock.scripps.edu/downloads/autodock-registration/autodock-4-2-download-page/

Huey, Ruth, Garrett M. Morris, Arthur J. Olson, and David S. Goodsell. 2007. “A Semiempirical Free Energy Force Field with Charge-Based Desolvation.” Journal of Computational Chemistry 28 (6): 1145–52. doi:10.1002/jcc.20634.

输出例子:

 1
 2
 3
 4
 5
 6
 7
 8
 9
10
11
12
13
14
15
Total Intermolecular Interaction Energy          =  -3.1862 kcal/mol
Total Intermolecular vdW + Hbond + desolv Energy =  -0.2499 kcal/mol
Total Intermolecular Electrostatic Energy        =  -2.9362 kcal/mol
Total Intermolecular + Intramolecular Energy     =  -5.6314 kcal/mol


epdb: USER    Estimated Free Energy of Binding    =   -1.40 kcal/mol  [=(1)+(2)+(3)-(4)]
epdb: USER    Estimated Inhibition Constant, Ki   =   94.72 mM (millimolar)  [Temperature = 298.15 K]
epdb: USER    
epdb: USER    (1) Final Intermolecular Energy     =   -3.19 kcal/mol
epdb: USER        vdW + Hbond + desolv Energy     =   -0.25 kcal/mol
epdb: USER        Electrostatic Energy            =   -2.94 kcal/mol
epdb: USER    (2) Final Total Internal Energy     =   -2.45 kcal/mol
epdb: USER    (3) Torsional Free Energy           =   +1.79 kcal/mol
epdb: USER    (4) Unbound System's Energy  [=(2)] =   -2.45 kcal/mol

版本:

1
AutoDock 4.2 Release 4.2.5.1 

AutoDock Vina

License: free, open-source (Apache license)

其为AutoDock的蛋白对接与在得分的继承者,其可以评价结合能力以及一些独有的项目,例如疏水贡献以及氢键(PS:译者并未发现有这些功能····)

网站:http://vina.scripps.edu/

O. Trott, A. J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, Journal of Computational Chemistry 31 (2010) 455-461

重新打分用法:

1
vina --config config.txt --score_only

config.txt的例子如下:

1
2
3
4
5
6
7
8
receptor = protein.pdbqt
ligand = ligand.pdbqt
center_x = -2.491 # Center of Grid points X
center_y = 30.038 # Center of Grid points Y
center_z = -10.765 # Center of Grid points Z
size_x = 25 # Number of Grid points in X direction
size_y = 25 # Number of Grid points in Y Direction
size_z = 25 # Number of Grid points in Z Direction

版本:

1
2
vina --version
AutoDock Vina 1.1.2 (May 11, 2011)

DrugScoreX

License: free without any limitations (redistribution requires permission)

DrugScoreX是一个较新的,对于蛋白配体打分具有比DrugScore更高精度的软件,其打分功能是基于统计势能?(statistical potentials)

网址:http://pc1664.pharmazie.uni-marburg.de/drugscore/

DSX: A Knowledge-Based Scoring Function for the Assessment of Protein–Ligand Complexes Gerd Neudert and Gerhard Klebe Journal of Chemical Information and Modeling 2011 51 (10), 2731-2745

用法:

 1
 2
 3
 4
 5
 6
 7
 8
 9
10
11
12
13
14
15
16
dsx_mac_64.mac -h

...

pro_file    :  A pdb or mol2 file of your protein.
              In pdb format metals in this file will be treated as part
              of the protein. => Be sure to delete metals in the pdb file
              if you want to supply some metals seperately (-M met_file)!
              All other HETATMs will be ignored!
              In mol2 format everything will be taken as part of the
              protein. => Be sure to delete molecules you want to supply
              seperately (-C, -W, -M) from the protein-mol2-file!
lig_file    :  A mol2- or autodock dlg-file containing all molecules that
              should be scored.
              
... 

译者注:其可以对金属离子进行打分

例子:

译者注:个人觉得作者下载的是mac版本

1
dsx_mac_64.mac -P protein.pdb -L ligand.mol2 -D pdb_pot_0511

其中pdb_pot_0511在下载文件中:

1
2
3
4
5
dsx/
	ACC_DON_AnD_HYD_ARO_map.def	
	mac64/ 			  # directory that contains the binaries
	README.txt			
	pdb_pot_0511/     # potentials

LigScore

License: free, open-source (GNU GPL)

与DrugScore的算法类似,提供本地(IMP 工具包)以及在线服务。 其得分功能具有两种"口味",RankScore,推荐被用于不同配体在蛋白结合界面的评分(例如虚拟筛选);PoseScore,在设置的一系列配体叠代中寻找优化的结合构象(例如相同的具有不同方向或者构象的配体)

网址:http://salilab.org/imp/ 在线网址:http://modbase.compbio.ucsf.edu/ligscore/

Fan H, Schneidman-Duhovny D, Irwin J, Dong GQ, Shoichet B, Sali A. Statistical Potential for Modeling and Ranking of Protein-Ligand Interactions. J Chem Inf Model. 2011, 51:3078-92.

使用:

1
2
ligand_score -h
Usage: ligand_score file.mol2 file.pdb [libfile]

其中protein_ligand_pose_score.lib 用来PoseScore打分,protein_ligand_rank_score.lib用来RankScore打分。

示例:

1
ligand_score my.mol2 my.pdb /usr/local/share/IMP/atom/protein_ligand_pose_score.lib

DOCK 6 Amber Score

License: Available free of charge for academic institutions, but there is a licensing fee for industrial organizations.

DOCK 6 是一个对接工具提供了几种打分函数,其可以用来对已经对接的构象进行再打分。下面是一个如何在打分的例子:

 1
 2
 3
 4
 5
 6
 7
 8
 9
10
11
12
13
14
dock6 -h



--------------------------------------
DOCK v6.7

Released February 2015
Copyright UCSF
--------------------------------------


Usage:
	dock6 -i filename.in [-o filename.out] [-v]

例子:

Amber 打分对蛋白配体复合物进行最小化,分子动力学模拟,能量最小化,更详细的计算方法可以查看:http://dock.compbio.ucsf.edu/DOCK_6/tutorials/amber_score/amber_score.htm

下面这个例子,我们假设一次已经进行了蛋白配体处理,例如:我们在蛋白PDB文件中移除了配体,金属离子和水分子,并且将组氨酸残基进行了正确的质子化。

1
prepare_amber.pl lig.mol2 1a9x.pdb

接下来我们创建如下的dock.in文件:

 1
 2
 3
 4
 5
 6
 7
 8
 9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
ligand_atom_file                                             lig.amber_score.mol2
limit_max_ligands                                            no
skip_molecule                                                no
read_mol_solvation                                           no
calculate_rmsd                                               no
use_database_filter                                          no
orient_ligand                                                no
use_internal_energy                                          no
flexible_ligand                                              no
bump_filter                                                  no
score_molecules                                              yes
contact_score_primary                                        no
contact_score_secondary                                      no
grid_score_primary                                           no
grid_score_secondary                                         no
multigrid_score_primary                                      no
multigrid_score_secondary                                    no
dock3.5_score_primary                                        no
dock3.5_score_secondary                                      no
continuous_score_primary                                     no
continuous_score_secondary                                   no
descriptor_score_primary                                     no
descriptor_score_secondary                                   no
gbsa_zou_score_primary                                       no
gbsa_zou_score_secondary                                     no
gbsa_hawkins_score_primary                                   no
gbsa_hawkins_score_secondary                                 no
SASA_descriptor_score_primary                                no
SASA_descriptor_score_secondary                              no
amber_score_primary                                          yes
amber_score_secondary                                        no
amber_score_receptor_file_prefix                             1a9x
amber_score_movable_region                                   ligand
amber_score_minimization_rmsgrad                             0.01
amber_score_before_md_minimization_cycles                    100
amber_score_md_steps                                         3000
amber_score_after_md_minimization_cycles                     100
amber_score_gb_model                                         5
amber_score_nonbonded_cutoff                                 18.0
amber_score_temperature                                      300.0
amber_score_abort_on_unprepped_ligand                        yes
ligand_outfile_prefix                                        output
write_orientations                                           no
num_scored_conformers                                        1
rank_ligands                                                 no

最后步骤,我们执行dock6读取dock.in文件

1
dock6 -i dock.in > dock.out 

dock.out文件,我们可以找到Amber 得分:

 1
 2
 3
 4
 5
 6
 7
 8
 9
10
11
12
13
14
15
16
17
[...]
Molecule: *****

Elapsed time for docking:  34 seconds

Anchors:       1
Orientations:      1
Conformations:     1

Amber Score:          -19.431744
    complex:        50250.946122
   receptor:       -50307.949484
     ligand:           37.571619


1 Molecules Processed
Total elapsed time: 41 seconds

蛋白文件和结构处理

OpenBabel

License: free, open-source (GNU GPL)

一个格式转换工具,具有本地编译包和多种语言的API

网站:http://openbabel.org/

O’Boyle, Noel M., Michael Banck, Craig A. James, Chris Morley, Tim Vandermeersch, and Geoffrey R. Hutchison. “Open Babel: An Open Chemical Toolbox.” J Cheminf 3 (2011): 33.

使用:

1
2
3
4
babel -H
Open Babel converts chemical structures from one file format to another

Usage: babel <input spec> <output spec> [Options]

例子:

1
babel -i mol2 my.mol2 -o pdbqt my.pdbqt

版本:

1
2
3
babel
No output file or format spec!
Open Babel 2.3.1 -- Oct 13 2011 -- 15:14:47

Reduce

License: free, but no particular license provided

一个加氢删氢的命令行工具,仅支持PDB格式

网站:http://kinemage.biochem.duke.edu/software/reduce.php

Word, et al.(1999) “Asparagine and glutamine: using hydrogen atom contacts in the choice of sidechain amide orientation” J. Mol. Biol. 285, 1735-1747.

使用:

 1
 2
 3
 4
 5
 6
 7
 8
 9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
~/Desktop >./reduce -h
reduce: version 3.23 05/21/2013, Copyright 1997-2013, J. Michael Word
reduce.3.23.130521
arguments: [-flags] filename or -

Suggested usage:
reduce -FLIP myfile.pdb > myfileFH.pdb (do NQH-flips)
reduce -NOFLIP myfile.pdb > myfileH.pdb (do NOT do NQH-flips)

Flags:
-FLIP             add H and rotate and flip NQH groups
-NOFLIP           add H and rotate groups with no NQH flips
-Trim             remove (rather than add) hydrogens

-NUClear          use nuclear X-H distances rather than default
                  electron cloud distances
-NOOH             remove hydrogens on OH and SH groups
-OH               add hydrogens on OH and SH groups (default)

-HIS              create NH hydrogens on HIS rings
-FLIPs            allow complete ASN, GLN and HIS sidechains to flip
                        (usually used with -HIS)
...

版本:

1
2
reduce -v
reduce.3.23.130521

配体结构

由于配体结构原文中主要是介绍的OpenEye,这个要求,所以就不 翻译了。

晶体结构分析

PyWater

一个寻找保守水分子的Pymol插件

文档与代码:https://github.com/hiteshpatel379/PyWATER

质谱?(Mass Spectrometry)

ProteoWizard

一个蛋白质组学分析的图形化和命令行分析工具 网站:http://proteowizard.sourceforge.net/index.shtml

OpenMS

一个LC/MS数据管理和分析C++工具包 网站:http://open-ms.sourceforge.net/ Marc Sturm, Andreas Bertsch, Clemens Gröpl, Andreas Hildebrandt, Rene Hussong, Eva Lange, Nico Pfeifer, Ole Schulz-Trieglaff, Alexandra Zerck, Knut Reinert, and Oliver Kohlbacher, 2008. “OpenMS – an Open-Source Software Framework for Mass Spectrometry” BMC Bioinformatics 9: 163. doi:10.1186/1471-2105-9-163.

(开发)库

Biopython

License: free, open-source (very permissive custom license) 一个Python工具包 网站:http://biopython.org/wiki/Main_Page 中文文档:http://biopython-cn.readthedocs.io/zh_CN/latest/

scikit-bio

License: free, open-source (BSD) 一个提供多种生物科学功能,数据结构和算法的Python包 网站:http://scikit-bio.org/

Licensed under CC BY-NC-SA 4.0