Subject: Re: De Novo Drug design

From: "Eric P. Wallis" <[email-masked]>
Date: Mon, 20 Dec 93 07:09:42 CST

Andy Holder makes some very valid points about the over selling of 
computational chemistry (CC).  The idea that CC can be used, without 
experimentation, to bring a product to production scale is ludicrous.  CC 
is a method that can help accelerate the research time and decrease the 
scale-up time as well as providing information when experimentation is not 
availible or accessible. Over selling of CC as an independent means of 
developing new products will only drive this method out of industry.

This is my $.02 on this subject.

On Fri, 17 Dec 1993 17:03:10 -0600 (CS, Andy Holder wrote:

>Hi Netters!
>
>I read with interest an earlier question requesting info about some 
>drugthat was designed from computational modelling.  About two years 
>ago, I asked for "semiempirical success" stories on thsi net and got a 
>rather low response.  Given my interest on a variety of fronts, I have 
>been thinking about this for sometime.  Please excuse the soapbox, but I 
>would like to share some of my thoughts and those of others I have 
>collected over the past few years on this issue:
>
>  Drug companies and other chemical manufacturers are not going to 
>tell you about this even if they have an example.  This type of stuff is 
>usually proprietary.
>
>  Is this really the correct question to ask about computational 
>chemistry (CC from here on)?  What is it that we expect CC to accomplish 
>for us?  Is it going to replace experimental investigations?
>
>  I look at CC in a company's product discovery cycle as a contributor to 
>the process, not an end in itself.  CC will NOT replace experimental 
>information or procedures.  We should not tell management (whether 
>scientific or "lay") that it will.  We should not try to sell it on 
>this basis.  The CC out there now is based on a set of models that are 
>imperfect.  These imperfections are present from molecular mechanics 
>through semiempirical to ab initio methods.  I admit they are getting 
>better and more reliable (I work quite hard along these lines myself in 
>the area of semiempirical methods) but they will never replace direct 
>observations.
>
>  How then should CC be viewed?  I think an excellent analogy is the way 
>we think about the analytical chemistry (AC) division of any large res-
>earch operation.   AC supports efforts in all phases of the research 
>process.  However, the mass spec guy is never asked "What specific drug 
>product is that there $500,000 GC/MS dohicky responsible for?"  Everyone
>recognizes that the mass spec is part of the effort, and things would be 
>crippled without it.
>
>  This is how CC should be integrated into the research/discovery process. 
>There are several models on how to include CC in a company's effort.  In 
>one, the CC guys are a consulting group that works with people that 
>bring them specific problems.  In another, each effort has one or more 
>CC guys IN the group.  Both are valid and both seem to be producing 
>results.  CC is good are predicting trends and in focusing experimental
>investigations, which are fairly expensive these days.  CC should be 
>part of every research problem in a modern setting.  PART, I said, not 
>WHOLE.
>
>  Alot of the recent "backlash" against CC is due to overselling.  If
>we CC folk expect to survive, we don't need to oversell the results that 
>we can provide, but honestly point out what CC should be doing.
>
>  To finish, I'll tell a little story.  When I was interviewing for a 
>job on leaving the Dewar group about 6 years ago, I visited the research 
>labs of a large midwestern polymer manufacturer.  I was shown a lab with 
>4 PhD polymer chemists in it.  Each was required to make 1 new polymer 
>blend per week.  These blends then went to physical testing for 
>evaluation as new products.  The company expected to get one new 
>CANDIDATE for a new product each year out of that lab.  Seems a bit
>cost prohibitive doesn't it?  They asked me how CC could help them.
>Back then, the answer was much less positive than it is now, but even 
>then, CC could have helped them focus their efforts more directly and
>greatly enhanced the "hit rate."  IMHO, that's what we do best.
>
>  Hope this wasn't too preachy.....
>
>
>
>   Andy Holder
>
>ps  I welcome comments from others, especially our industrial brethren.
>
>=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
>                              DR. ANDREW HOLDER
>             Assistant Professor of Computational/Organic Chemistry
>
>Department of Chemistry              ||  BITNET Addr:   AHOLDER@UMKCVAX1
>University of Missouri - Kansas City ||  Internet Addr: [email-masked]
>Spencer Chemistry, Room 315          ||  Phone Number:  (816) 235-2293
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Dr. Eric P. Wallis
Computational Chemistry
Phillips Petroleum Co.      (918) 661-7956  Voice
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