From chemistry-request@ccl.net Wed Mar  4 10:36:29 1992
Date: Wed, 4 Mar 92 09:40:36 EST
From: states@ncbi.nlm.nih.GOV (David States)
Subject: Re: A gadfly forever..... (How far can you push semi-empirical
To: CHEMISTRY@ccl.net, AHOLDER@VAX1.UMKC.EDU
Status: RO

|>  Andy Holder writes:
|>
|>   ... I think the discussion should refocus
|>   on "What can be done now that couldn't be done before?"  Semi-
|>   empirical methods can now do calculations on reasonably sized
|>   polymer chains or biomolecules efficiently.

To me this is a real opportunity.  Empirical energy simulations of
biological macromolecules have improved incrementally over the past
decade, but many significant terms in the potential energy function are
ignored, particularly polarization effects (charge induced dipole
terms, cooperativity in hydrogen bonding etc.).  These terms are
significant compared to kT.  It does not make alot of sense to me to
run longer and longer simulations when you know the underlying
potential function is flawed.  Semi-empirical methods offer a real
hope of addressing some of these issues.

So what are the largest peptide systems that have been evaluated
with semi-empirical methods?  

Have any been done with Monte Carlo averaging over nuclear conformations?

Has anyone been bold enough to attempt dynamical simulations based
on semi-empirical PE functions and derivatives?

David States
National Center for Biotechnology Information / National Library of Medicine