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:
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:
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····)
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:
vina --config config.txt --score_only
config.txt的例子如下:
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:
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:
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
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:
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:
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:
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:
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。
prepare_amber.pl lig.mol2 1a9x.pdb
接下来我们创建如下的dock.in文件:
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
dock6 -i dock.in > dock.out
在dock.out文件，我们可以找到Amber 得分:
[...]
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
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:
babel -H
Open Babel converts chemical structures from one file format to another
Usage: babel <input spec> <output spec> [Options]
例子:
babel -i mol2 my.mol2 -o pdbqt my.pdbqt
版本:
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:
~/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:
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/
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