同源建模总结(一） automodel类的使用

一：自动建模的过程中包含水分子，配体残基和氢原子

如果你的模板序列中包含配体或非蛋白残基，你可以在".ali"文件中通过在模板序列和待建序列的末尾加点"."来表示，当然在执行的脚本中还要加上语句env.io.hetatm=True,默认情况下不会处理HETATM的原子。

Example: examples/automodel/model-ligand.py

# Homology modeling with ligand transfer from the templatefrom modeller import *              # Load standard Modeller classesfrom modeller.automodel import *    # Load the automodel classlog.verbose()    # request verbose outputenv = environ()  # create a new MODELLER environment to build this model in# directories for input atom filesenv.io.atom_files_directory = ['.', '../atom_files']# Read in HETATM records from template PDBsenv.io.hetatm = Truea = automodel(env,              alnfile  = 'align-ligand.ali',  # alignment filename              knowns   = '5fd1',              # codes of the templates              sequence = '1fdx')              # code of the targeta.starting_model= 4                 # index of the first modela.ending_model  = 4                 # index of the last model                                    # (determines how many models to calculate)a.make()                            # do the actual homology modeling

Example: examples/automodel/align-ligand.ali

C; Similar to alignment.ali, but with ligands included>P1;5fd1structureX:5fd1:1    :A:108  :A:ferredoxin:Azotobacter vinelandii: 1.90: 0.19AFVVTDNCIKCKYTDCVEVCPVDCFYEGPNFLVIHPDECIDCALCEPECPAQAIFSEDEVPEDMQEFIQLNAELAEVWPNITEKKDPLPDAEDWDGVKGKLQHLER..*>P1;1fdxsequence:1fdx:1    : :56   : :ferredoxin:Peptococcus aerogenes: 2.00:-1.00AYVINDSC--IACGACKPECPVNIIQGS--IYAIDADSCIDCGSCASVCPVGAPNPED------------------------------------------------..*

上面中的每个"."代表一个HETATM的残基，如果你有多个模板的话，只想要其中一个模板的配体作为建模的配体，那么可以将其他模板的对应的配体的残基改为"-".

如果想保留模板中的水分子，则需要在模板序列和待建序列中加入"w"字母，并且需要设置env.io.water=True.

如果想在待建序列中加入H原子，则需要在设置env.io.hydrogen=True.

二：对构建出的模型进行优化（更改默认的优化过程）

# Example of changing the default optmization schedulefrom modeller import *from modeller.automodel import *log.verbose()env = environ()# Give less weight to all soft-sphere restraints:env.schedule_scale = physical.values(default=1.0, soft_sphere=0.7)env.io.atom_files_directory = ['.', '../atom_files']a = automodel(env, alnfile='alignment.ali', knowns='5fd1', sequence='1fdx')a.starting_model = a.ending_model = 1#建好模型后的优化过程
# Very thorough VTFM optimization:a.library_schedule = autosched.slowa.max_var_iterations = 300# Thorough MD optimization:a.md_level = refine.slow# Repeat the whole cycle 2 times and do not stop unless obj.func. > 1E6a.repeat_optimization = 2a.max_molpdf = 1e6a.make()
 
三：利用多个模板来构建出一个模型
Example: examples/automodel/model-multiple.py 
# Homology modeling with multiple templatesfrom modeller import *              # Load standard Modeller classesfrom modeller.automodel import *    # Load the automodel classlog.verbose()    # request verbose outputenv = environ()  # create a new MODELLER environment to build this model in# directories for input atom filesenv.io.atom_files_directory = ['.', '../atom_files']a = automodel(env,              alnfile  = 'align-multiple.ali', # alignment filename              knowns   = ('5fd1', '1bqx'),     # codes of the templates              sequence = '1fdx')               # code of the targeta.starting_model= 1                 # index of the first modela.ending_model  = 1                 # index of the last model                                    # (determines how many models to calculate)a.make()                            # do the actual homology modeling
 
Example: examples/automodel/align-multiple.ali 
>P1;5fd1structureX:5fd1:1    :A:106  :A:ferredoxin:Azotobacter vinelandii: 1.90: 0.19AFVVTDNCIKCKYTDCVEVCPVDCFYEGPNFLVIHPDECIDCALCEPECPAQAIFSEDEVPEDMQEFIQLNAELAEVWPNITEKKDPLPDAEDWDGVKGKLQHLER*>P1;1bqxstructureN:1bqx:   1 :A: 77  :A:ferredoxin:Bacillus schlegelii:-1.00:-1.00AYVITEPCIGTKCASCVEVCPVDCIHEGEDQYYIDPDVCIDCGACEAVCPVSAIYHEDFVPEEWKSYIQKNRDFFKK-----------------------------*>P1;1fdxsequence:1fdx:1    : :54   : :ferredoxin:Peptococcus aerogenes: 2.00:-1.00AYVINDSC--IACGACKPECPVNIIQGS--IYAIDADSCIDCGSCASVCPVGAPNPED------------------------------------------------*
 
四：使用automodel.residue_range()来优化所建模型的部分残基
# Homology modeling by the automodel class## Demonstrates how to refine only a part of the model.## You may want to use the more exhaustive "loop" modeling routines instead.#from modeller import *from modeller.automodel import *    # Load the automodel classlog.verbose()# Override the 'select_atoms' routine in the 'automodel' class:# (To build an all-hydrogen model, derive from allhmodel rather than automodel# here.)class MyModel(automodel):    def select_atoms(self):        # Select residues 1 and 2 (PDB numbering)        return selection(self.residue_range('1:', '2:'))        # The same thing from chain A (required for multi-chain models):        # return selection(self.residue_range('1:A', '2:A'))        # Residues 4, 6, 10:        # return selection(self.residues['4'], self.residues['6'],        #                  self.residues['10'])        # All residues except 1-5:        # return selection(self) - selection(self.residue_range('1', '5'))env = environ()# directories for input atom filesenv.io.atom_files_directory = ['.', '../atom_files']# selected atoms do not feel the neighborhoodenv.edat.nonbonded_sel_atoms = 2# Be sure to use 'MyModel' rather than 'automodel' here!a = MyModel(env,            alnfile  = 'alignment.ali',     # alignment filename            knowns   = '5fd1',              # codes of the templates            sequence = '1fdx')              # code of the targeta.starting_model= 3                # index of the first modela.ending_model  = 3                # index of the last model                                   # (determines how many models to calculate)a.make()                           # do homology modeling
 
五：模拟过程中包含二硫键
默认情况下automodel会自动的产生适当的二硫键的限制，这通过使用model.patch_ss_templates()函数。
手动的添加二硫键的限制可以通过使用model.patch()函数，这个函数调用CHARMM的拓扑文件“DISU”来修补残基。
# Homology modeling by the automodel classfrom modeller import *              # Load standard Modeller classesfrom modeller.automodel import *    # Load the automodel class# Redefine the special_patches routine to include the additional disulfides# (this routine is empty by default):class MyModel(automodel):    def special_patches(self, aln):        # A disulfide between residues 8 and 45:        self.patch(residue_type='DISU', residues=(self.residues['8'],                                                  self.residues['45']))log.verbose()    # request verbose outputenv = environ()  # create a new MODELLER environment to build this model in# directories for input atom filesenv.io.atom_files_directory = ['.', '../atom_files']a = MyModel(env,            alnfile  = 'alignment.ali',     # alignment filename            knowns   = '5fd1',              # codes of the templates            sequence = '1fdx')              # code of the targeta.starting_model= 1                 # index of the first modela.ending_model  = 1                 # index of the last model                                    # (determines how many models to calculate)a.make()                            # do the actual homology modeling