非常有用的蛋白質科學工具與專案

weixin_34194087發表於2017-06-21

翻譯自，github:(2015版)

蛋白配體對接與評價

AutoDock 4.2

License:free, open-source (GNU GPL)

一個使用相對廉價的"hybrid"力場的分子對接與得分工具，該力場為半經驗的方法（molecular mechanics as well as empirical terms）.其預測的絕對結合自由能相較於更大的計算量專案可能精確度較低，但這種半經驗方法對於相對得分(ranking)可能更加合適。

雖然AutoDock這種半經驗力場被AutoDock Vina這個完整的基於知識的，統計得分函式的軟體所替代。同時AutoDock Vina具有更精確和更快的速度。但是AutoDock 4.2 提供了更加詳細的輸出描述可能對某些應用具有其獨有的優勢。

網址: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.

輸出例子:

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)

其為AutoDock的蛋白對接與在得分的繼承者，其可以評價結合能力以及一些獨有的專案，例如疏水貢獻以及氫鍵(PS:譯者並未發現有這些功能····)

網站: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:

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是一個較新的，對於蛋白配體打分具有比DrugScore更高精度的軟體，其打分功能是基於統計勢能？(statistical potentials)

網址: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.
              
...

譯者注:其可以對金屬離子進行打分

例子:

譯者注:個人覺得作者下載的是mac版本

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

其中pdb_pot_0511在下載檔案中:

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)

與DrugScore的演算法類似,提供本地(IMP 工具包)以及線上服務。
其得分功能具有兩種"口味",RankScore，推薦被用於不同配體在蛋白結合介面的評分(例如虛擬篩選);PoseScore，在設定的一系列配體疊代中尋找優化的結合構象(例如相同的具有不同方向或者構象的配體)

網址:http://salilab.org/imp/
線上網址: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 用來PoseScore打分，protein_ligand_rank_score.lib用來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 是一個對接工具提供了幾種打分函式，其可以用來對已經對接的構象進行再打分。下面是一個如何在打分的例子:

dock6 -h



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

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


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

例子:

Amber 打分對蛋白配體複合物進行最小化，分子動力學模擬，能量最小化，更詳細的計算方法可以檢視:http://dock.compbio.ucsf.edu/DOCK_6/tutorials/amber_score/amber_score.htm

下面這個例子，我們假設一次已經進行了蛋白配體處理，例如:我們在蛋白PDB檔案中移除了配體，金屬離子和水分子，並且將組氨酸殘基進行了正確的質子化。

prepare_amber.pl lig.mol2 1a9x.pdb

接下來我們建立如下的dock.in檔案:

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

最後步驟，我們執行dock6讀取dock.in檔案

dock6 -i dock.in > dock.out

在dock.out檔案，我們可以找到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

蛋白檔案和結構處理

OpenBabel

License: free, open-source (GNU GPL)

一個格式轉換工具，具有本地編譯包和多種語言的API

網站: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:

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

一個加氫刪氫的命令列工具，僅支援PDB格式

網站: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

配體結構

由於配體結構原文中主要是介紹的OpenEye，這個要求，所以就不 翻譯了。

晶體結構分析

PyWater

一個尋找保守水分子的Pymol外掛

文件與程式碼:https://github.com/hiteshpatel379/PyWATER

質譜?(Mass Spectrometry)

ProteoWizard

一個蛋白質組學分析的圖形化和命令列分析工具
網站:http://proteowizard.sourceforge.net/index.shtml

OpenMS

一個LC/MS資料管理和分析C++工具包
網站: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.

（開發）庫

Biopython

License: free, open-source (very permissive custom license)
一個Python工具包
網站:http://biopython.org/wiki/Main_Page
中文文件:http://biopython-cn.readthedocs.io/zh_CN/latest/

scikit-bio

License: free, open-source (BSD)
一個提供多種生物科學功能，資料結構和演算法的Python包
網站:http://scikit-bio.org/

更多原創精彩視訊敬請關注生信雜談:

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