📄 faq.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">Frequently Asked Questions</h2>
<hr>
<p> We have collected some FAQs on LigBuilder
in the following section. Hope they will help you to use
LigBuilder. If these FAQs still do not cover your question,
please feel free to contact us at:</p>
<div align="center"><center>
<address>
Prof. Luhua Lai <br>
Institute of Physical Chemistry, Peking University<br>
Beijing 100871, P.R.China <br>
E-mail: <a href="mailto:lai@ipc.pku.edu.cn">lai@ipc.pku.edu.cn</a>
Fax: 86-10-62751725
</address>
</center></div>
<hr>
<ol>
<li><a href="#subject_1">What is new in LigBuilder v1.2?</a></li>
<li><a href="#subject_2">Can I use LigBuilder for DNA-based
drug design?</a></li>
<li><a href="#subject_3">Why do I get no result in a GROW
job?</a></li>
<li><a href="#subject_4">Why do I get no result in a LINK
job?</a></li>
<li><a href="#subject_5">How can I estimate the binding
affinity of a single ligand molecule?</a></li>
<li><a href="#subject_6">How can I estimate the LogP value of
a single molecule?</a></li>
<li><a href="#subject_7">How to use LigBuilder wisely?</a></li>
</ol>
<hr>
<h4><a name="subject_1"><font color="#0000FF">1. What is new in
LigBuilder v1.2?</font></a></h4>
<p> LigBuilder first became available to the
public in September, 1999. Since then, we have registered
hundreds of users. As feedback, these users point out the bugs in
the LigBuilder program and also make all kinds of comments and
suggestion. All of these have been pushing us to go ahead.</p>
<p> The latest version is LigBuilder v1.2.
Besides bug-fixing, major improvements include: </p>
<p> (1) As in the former versions, the final
results will be selected only from the last generation. There
are, at least, two major drawbacks by doing so: (i) all the
molecules generated in other generations are wasted! (ii) the
user may have difficulty in determining the proper "<font
color="#000000">NUMBER_OF_GENERATION</font>" since only the
last generation is considered for output. In LigBuilder v1.2,
every each molecule that meets the user's criteria will be
collected as result, no matter from which generation it comes.
Therefore, the user does not have to worry about choosing a
proper "<font color="#000000">NUMBER_OF_GENERATION</font>"
any more --- just set a fairly large number for it.</p>
<p> (2) We used to provide both
"generational-replacement" and "steady-state"
GA modes for GROW and LINK. However, We found that this is more
confusing rather than helpful since most users cannot tell the
difference between these two modes. After extensive testing, now
we believe "generational-replacement" is more suitable
for the growing strategy while "steady-state" is more
suitable for the linking strategy. Therefore, in LigBuilder v1.2,
GROW is run only under the "generational-replacement"
mode while LINK is run under the "steady-state" mode.</p>
<p> (3) In LigBuilder v1.2, we have added a new
module, PROCESS. The basic function of PROCESS is analyzing and
extracting molecules from a LigBuilder LIG file. This function
used to be included in GROW and LINK. By developing this function
into a separated module, more flexibility is introduced into the
application of LigBuilder.</p>
<p> (4) We have re-designed the structural
manipulating algorithms to make them more efficient. The running
time, especially for GROW, has been largely reduced.</p>
<p> (5) The user's manual is rewritten.
Besides, our paper describing LigBuilder has been published: <a
href="ligbuilder.pdf">Wang, R.; Gao, Y.; Lai, L.
"LigBuilder: A Multiple-Purpose Program for Structure-Based
Drug Design", <em>J.Mol.Model</em>., <strong>2000</strong>, <em>6</em>,
498-516.</a> So now you will not have problem in citing
LigBuilder.</p>
<hr>
<h4><a name="subject_2"><font color="#0000FF">2. Can I use
LigBuilder for DNA-based drug design?</font></a></h4>
<p> The answer is "NO". Although
DNA-based drug design shares the same concepts with protein-based
drug design, there are two reasons preventing you from directly
applying LigBuilder to such a project: (1) New parameters are
necessary for estimating the DNA-ligand interactions; (2) The
binding site of a DNA (minor groove) is more open than a protein
(usually a pocket), therefore the construction strategy may also
need to be adjusted.</p>
<hr>
<h4><a name="subject_3"><font color="#0000FF">3. Why do I get no
result in a GROW job?</font></a></h4>
<p><font color="#000000"> This is not so easy
to interpret. However, the most likely reason is: you have set
something wrong. Did you dock the seed into the binding pocket?
Did you assign proper growing sites on the seed? Did you edit the
building block library correctly? Did you set up the chemical
rules too strict so actually no molecule can satisfy them? If the
program still gives no result because of some mysterious reasons,
please let us know.</font></p>
<hr>
<h4><a name="subject_4"><font color="#0000FF">4. Why do I get no
result in a LINK job?</font></a></h4>
<p> This is not easy to interpret either.
So please make sure that everything is correct: the seed, the
building block library, the chemical rules, and all the other
parameters. </p>
<p> But there is one thing we should
mention here: the linking algorithm is more complicated than the
growing algorithm. Linking between two separated structures will
happen only when both conformation and chemistry are proper.
Therefore, LINK usually gives less results than GROW does. Since
the seed structure for LINK usually contains several chemical
fragments, it is also possible that no reasonable linkage between
them can be made because their positions or orientations are not
"proper". So if this does happen, please modify your
seed structure. Leave enough space between each fragment is a
good idea.</p>
<hr>
<h4><a name="subject_5"><font color="#0000FF">5. How can I
estimate the binding affinity of a single ligand molecule?</font></a></h4>
<p> Maybe you have noticed that LigBuilder
gives estimation of the binding affinities of the resultant
molecules. It does so by using the SCORE algorithm: <a
href="score.pdf">Wang, R.; Liu, L.; Lai, L.; Tang, Y.
"SCORE: A new empirical method for estimating the binding
affinity of a protein-ligand complex", <em>J.Mol.Model</em>.,
<strong>1998</strong>, <em>4</em>, 379-394.</a> If you want to
estimate the binding affinity of a single ligand molecule to its
receptor protein, you may download the <font color="#FF0000">SCORE</font>
program from our FTP server:
ftp://ftp2.ipc.pku.edu.cn/pub/software/score/.</p>
<hr>
<h4><a name="subject_6"><font color="#0000FF">6. How can I
estimate the LogP value of a single molecule?</font></a></h4>
<p> LigBuilder also estimates the octanol/water
partition coefficients of the resultant molecules. It does so by
using the XLOGP algorithm: <a href="xlogp2.pdf">Wang, R.; Gao,
Y.; Lai, L. "Calculating partition coefficient by
atom-additive method", <em>Perspectives in Drug Design and
Discovery</em>, <strong>2000</strong>, <em>19</em>, 47-66</a>. If
you want to estimate the LogP value of a single molecule, you may
download the <font color="#FF0000">XLOGP</font> program from our
FTP server: ftp://ftp2.ipc.pku.edu.cn/pub/software/xlogp/.</p>
<hr>
<h4><a name="subject_7"><font color="#0000FF">7. How to use
LigBuilder wisely?</font></a></h4>
<p> Good question! </p>
<p> LigBuilder is a multiple-purposed
structure-based drug design program. It provides the abilities
for binding pocket analyzing, lead discovery and lead
optimization. The modularized structure of LigBuilder enhances
the flexibility in its application. Besides, it is very easy to
use --- the users like this so much.</p>
<p> However, please remember: do not use it as
a black box; use it as an idea generator for instead. At least at
present drug design is not computer-done but computer-aided.
Especially when analyzing the final results given by LigBuilder,
we do believe that expertise is still very important. The major
drawback of LigBuilder is that, sometimes, it gives molecules
which are not synthetically feasible. In this case, you are
encouraged to tailor those molecules if necessary.</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> <a href="grow.html">[GROW]</a>
<a href="link.html">[LINK]</a> <a href="process.html">[PROCESS]</a>
<a href="skill.html">[Skills]</a> [FAQs]</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 + -