📄 grow.html
字号:
<html>
<head>
<meta http-equiv="Content-Type"
content="text/html; charset=iso-8859-1">
<meta name="GENERATOR" content="Microsoft FrontPage Express 2.0">
<title>User manual for LigBuilder v1.2</title>
</head>
<body background="background.gif" bgcolor="#FFFFFF">
<p align="center"><img src="title.gif"
alt="title.gif (27521 bytes)" width="480" height="160"></p>
<h2 align="center">How to use LigBuilder: GROW </h2>
<hr>
<p> The major function of GROW is constructing
ligand molecules for the target protein by applying the growing
strategy. All the molecules are originated from a
"seed" structure and they are developed and evolved
with a Genetic Algorithm procedure. All resultant molecules will
be collected in a file.</p>
<p> Synopsis of running GROW:</p>
<p> <font
color="#FF0000"><strong>grow parameter_file</strong></font></p>
<p> For example:</p>
<p> grow
grow.index </p>
<p> The parameter file assembles all the
information necessary to run GROW as you wish. You should edit
the parameter file before running GROW. The key words appeared in
this parameter file are explained in the following.</p>
<p> First, tell the program about the input
files:</p>
<p> <font color="#0000FF">SEED_LIGAND_FILE</font>:
The Mol2 file presenting the "<font color="#0000FF">seed</font>"
structure. As mentioned above, this is absolutely necessary
because the "seed" is the mother of all the resultant
molecules. Therefore, it will be ideal if the seed structure
holds the key features of the prospective ligands. LigBuilder
itself does not provide a program to generate the seed structure
so you need to prepare it yourself. For more instruction of how
to prepare a seed structure, please refer to the <a
href="skill.html#subject_1">Advanced Skills</a> section.</p>
<p> <font color="#0000FF">POCKET_ATOM_FILE</font>:
The corresponding file given by POCKET.</p>
<p> <font color="#0000FF">POCKET_GRID_FILE</font>:
The corresponding file given by POCKET.</p>
<p> <font color="#0000FF">PARAMETER_DIRECTORY</font>:
The path of the directory "<font color="#0000FF">parameter</font>".
Under this directory, there are force field parameters used by
LigBuilder. Parameters for atoms, bonds, and torsions are cited
from Tripos force field. This directory is used by POCKET, GROW,
LINK and PROCESS.</p>
<p> Then, there are the definitions of three
fragment libraries:</p>
<p> <font color="#0000FF">BUILDING_BLOCK_LIBRARY</font>:
The path of the building-block fragment library. The default one
is "<font color="#0000FF">fragment.mdb</font>".</p>
<p> <font color="#0000FF">FORBIDDEN_STRUCTURE_LIBRARY</font>:
The path of the forbidden substructure library. The default one
is "<font color="#0000FF">forbidden.mdb</font>".</p>
<p> <font color="#0000FF">TOXIC_STRUCTURE_LIBRARY</font>:
The path of the toxic substructure library. The default one is
"<font color="#0000FF">toxicity.mdb</font>".</p>
<p> If you are a novice to LigBuilder, you can
simply adopt the default settings for the above three fragment
libraries. If you want to learn how to edit them to meet your own
purpose, please refer to the <a href="skill.html">Advanced Skills</a>
section.</p>
<p> GROW builds up molecules with three kinds
of manipulations, i.e. growing, linking, and mutation. The
following three parameters will control how much these
manipulations will be applied, respectively:</p>
<p> <font color="#0000FF">GROWING_PROBABILITY</font>:
For the current version of GROW, growing manipulation is the
essential manipulation. So please fix this parameter to 1.00.</p>
<p> <font color="#0000FF">LINKING_PROBABILITY</font>:
For GROW, linking manipulation will result in intramolecular
rings whenever it is possible. This manipulation is relatively
slow so this parameter will affect the overall running time
significantly. We recommend this parameter to be 0.50.</p>
<p> <font color="#0000FF">MUTATION_PROBABILITY</font>:
GROW also employs a "smart mutation" manipulation to
improve the binding affinity of ligand molecules. We recommend
this parameter to be 0.50.</p>
<p> Then there are a set of chemical viability
rules, including "<font color="#0000FF">APPLY_CHEMICAL_RULES</font>",
"<font color="#0000FF">APPLY_FORBIDDEN_STRUCTURE_CHECK</font>",
"<font color="#0000FF">APPLY_TOXIC_STRUCTURE_CHECK</font>",
"<font color="#0000FF">MAXIMAL_MOLECULAR_WEIGHT</font>",
"<font color="#0000FF">MINIMAL_MOLECULAR_WEIGHT</font>",
"<font color="#0000FF">MAXIMAL_LOGP</font>", "<font
color="#0000FF">MINIMAL_LOGP</font>", "<font
color="#0000FF">MAXIMAL_HB_DONOR_ATOM</font>", "<font
color="#0000FF">MINIMAL_HB_DONOR_ATOM</font>", "<font
color="#0000FF">MAXIMAL_HB_ACCEPTOR_ATOM</font>", "<font
color="#0000FF">MINIMAL_HB_ACCEPTOR_ATOM</font>", "<font
color="#0000FF">MAXIMAL_PKD</font>", and "<font
color="#0000FF">MINIMAL_PKD</font>". To learn what these
parameters mean and how to set them, please refer to the <a
href="skill.html#subject_2">Advanced Skills </a>Section.</p>
<p> GROW uses Genetic Algorithm (GA) to develop
and evolve molecules. It is run under <font color="#0000FF">generational-replacement</font><font
color="#FF0000"> </font><font color="#000000">mode. </font>The
rough procedure is like this: (1) Generate the initial population
based on the seed structure; (2) Choosing "parents"
molecules from the current population into the mating pool; (3)
Copy the "elite" of the current population into the new
population; (4) Fill out the new population by performing
structural manipulations on the molecules in the mating pool. (5)
Go to Step 2 until the pre-set number of generations has been
reached.</p>
<p align="center"><img src="ga_gr.gif" width="402" height="232"></p>
<p align="center"><font color="#000080">Flow chart of the GA
procedure implemented in GROW</font></p>
<p> Therefore, there are a few parameters for
setting up this GA procedure:</p>
<p> <font color="#0000FF">NUMBER_OF_GENERATION:
</font><font color="#000000">Number of generations (GA circle) to
go through. Typically 10~20 generations will be enough.</font></p>
<p> <font color="#0000FF">NUMBER_OF_POPULATION:
</font><font color="#000000">Size of the population. This
parameter determines dominatingly how much memory the program
will take while running. Usually it is several thousands.</font></p>
<p> <font color="#0000FF">NUMBER_OF_PARENTS: </font><font
color="#000000">Number of molecules to be selected into the
mating pool. We recommend the ratio of NUMBER_OF_POPULATION /
NUMBER_OF_PARENTS should be larger than 10.</font></p>
<p> <font color="#0000FF">SIMILARITY_CUTOFF: </font>Maximal
similarity between any two molecules in the mating pool. For
instance, if it is set to 1.00, it means duplicates are not
allowed to exist. By setting this parameter, you will exert a
forced diversity in the mating pool and thus are more likely to
get more diverse offspring. The lower this parameter is, the
higher diversity will be achieved. We recommend this parameter to
be 0.80~1.00.</p>
<p> <font color="#0000FF">ELITISM_RATIO: </font><font
color="#000000">Percentage of "elitism". </font>This
parameter could be between 0 and 1. For example, if it is set to
0.10, that means the top 10% of the current population will be
copied directly to the new population. By doing so, the elite
molecules will not lose by accident. We recommend this parameter
to be around 0.10.</p>
<p> <font color="#000000">A "typical"
set of the above parameters could be: NUMBER_OF_GENERATION = 20;
NUMBER_OF_POPULATION = 3000; NUMBER_OF_PARENTS = 200;
SIMILARITY_CUTOFF = 0.90; ELITISM_RATIO = 0.10. But of course you
can change them according to the requests of your project or the
capacity of your computer.</font></p>
<p> The last two items in the parameter file
are concerning with the outputs:</p>
<p> <font color="#0000FF">POPULATION_RECORD_FILE</font>:
This file will record the final population in LigBuilder LIG
format. It provides the possibility of resuming a former job.
This is explained in the <a href="skill.html#subject_6">Advanced
Skills</a> section.</p>
<p> <font color="#0000FF">LIGAND_COLLECTION_FILE
</font>: This is the output file of GROW. During the GA
procedure, all the molecules which meet the chemical rules you
set above will be collected into this file. It is in LigBuilder
LIG format so it can be analyzed by PROCESS. Please notice that
these molecules will not come only from the final generation (as
in the former version of LigBuilder) but from every generation.
It forms a structure-based virtual library for the target
protein.</p>
<p> Running GROW takes much more time than
running POCKET or PROCESS because it does the major job. If run
on a SGI O2/R10000/150M workstation, a typical GROW job will take
several hours. The overall running time is roughly proportional
to the number of GA generations and the size of the population.</p>
<hr>
<p align="center"><a href="index.html">[Content]</a> <a
href="intro.html">[Introduction]</a> <a href="download.html">[Download]</a>
<a href="install.html">[Install]</a> <a href="overview.html">[Overview]</a>
<a href="pocket.html">[POCKET]</a> [GROW] <a href="link.html">[LINK]</a>
<a href="process.html">[PROCESS]</a> <a href="skill.html">[Skills]</a>
<a href="faq.html">[FAQs]</a></p>
<p align="center"><font size="2"><em>(These web pages are edited
by Dr. Renxiao Wang. Latest update: August, 2000)</em></font></p>
</body>
</html>
⌨️ 快捷键说明
复制代码
Ctrl + C
搜索代码
Ctrl + F
全屏模式
F11
切换主题
Ctrl + Shift + D
显示快捷键
?
增大字号
Ctrl + =
减小字号
Ctrl + -