非常有用的蛋白质科学工具与项目

翻译自，github:https://github.com/rasbt/protein-science/blob/master/scripts-and-tools/more_protein-science_tools.md(2015版)

微信中可能有些错位，可以点击原文阅读进入简书查看

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····)

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:

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 v6.7Released February 2015Copyright 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                                                noread_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                             0.01amber_score_before_md_minimization_cycles                    100amber_score_md_steps                                         3000amber_score_after_md_minimization_cycles                     100amber_score_gb_model                                         5amber_score_nonbonded_cutoff                                 18.0amber_score_temperature                                      300.0amber_score_abort_on_unprepped_ligand                        yes
ligand_outfile_prefix                                        output
write_orientations                                           no
num_scored_conformers                                        1rank_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:       1O
rientations:      1
Conformations:     1

Amber Score:          -19.431744
    complex:        50250.946122
   receptor:       -50307.949484
     ligand:           37.5716191 Molecules Processed
Total elapsed time: 41 seconds

蛋白文件和结构处理

OpenBabel

License: free, open-source (GNU GPL)