Re: vit D --- in silico modeling of receptor-ligand affinities

[Guest guest]

on M P dot com there is also some information and links to tools. The

programs are free, the trick is to know what to look

for. There is also a DVD presentation for affinities between differnt

receptors.

This is what TM presented on DMM2006 in stockholm.

/Per

wrote:

>Some may be interested in recent reports of computer-calculated

>binding affinities between the VDR and two of its ligands, the 25-OH-

>vitD and 1,25-(OH)2-vitD steroids.

>

>Where does the reliability of this sort of in silico technology

>stand, one might wonder, in comparison with old-fashioned in vitro

>assays. I'm absolutely not well-informed on the subject and havent

>really read the abovementioned recent reports. And I will readily

>admit I havent been very happy about the consistency of results I've

>seen for the very few such in vitro assays I've looked at (reguarding

>the binding affinites of tetracyclines).

>

>That said, its interesting to read the following post by Lowe,

>re a recent paper finding that these sort of in silico simulations

>are generally a long way from hot in terms of reliability:

>

>http://pipeline.corante.com/archives/2005/11/01/molecular_modeling_cag

>e_match.php

>

>Lowe is a medicinal chemist whose fascinating blog I got to via a

>link from Norman. I havent read the paper he discusses.

>

>

[Guest guest]

> There is also a DVD presentation for affinities between differnt

> receptors.

> This is what TM presented on DMM2006 in stockholm.

> /Per

But does in silico modeling provide strong evidence for whatever he

said?

Lowe has in fact a whole subject heading devoted to such modeling,

with several posts and numerous comments. (Not just the post I linked

to.)

http://pipeline.corante.com/archives/in_silico/

He (perhaps along with many of his readers) is a drug lead

optimization synthetic chemist - someone who contemplates and cooks

up hundreds or thousands of variants of a candidate drug, for his

firms biologists to test in hopes of finding improved safety and/or

efficacy. This work could largely be done by a computer if excellent

in silico modeling were to become broadly applicable. Thus, its

possible he could have a touch of a bias or natural hostility to in

silico modeling because of what he does as a job.

On the other hand, if current in silico modeling were so great I

imagine we would be hearing about people like Lowe losing their jobs.

That doesnt seem to be taking place.