Subject: REPLY TO GLOBAL MIN. QUESTION

From: "E. Lewars" <[email-masked]>
Date: Sun, 9 Apr 1995 13:36:24 -0400

1995 April 8

Shubin Liu ([email-masked]) asked how one can be sure he has found the
global, rather than merely a local, minimum.  I think there is no short answer
to this question.  If you are looking at something like water or methane, where
everyone knows in a general way what the answer looks like, there is no
ambiguity (what's the n-fold analog of an ambiguity?), and you might even
dispense with the frequency job which is usually considered prudent to
characterize a stationary state.  But note that even very simple molecules can
have PES's with >1 minimum.
    If you are working with proteins I suspect that at the current state of
the art you may as well forget about nailing down the global minimum.  Somewhere
between water and a peptide you can worry about finding the global min. If, as
is usually the case, the various possible minima you are concerned about arise
from conformational possibilities, the systematic way to look for the global
one is with a conformational search program as implemented in several commercial
packages, e.g. Spartan.  If you have no hangups about gambling, there is at least
one stochastic search program, PCGlobal, from Serena Software, which randomly
generates a slew of input structures, hopefully including some you may not have
thought of.  If your molecule is not too big you could do the job by hand,
using input structures corresponding to all reasonable-looking possibilities
for minima; your computational chemistry program should slide each one into
the nearest minimum for the level you're using; if size doesn't make it
impractical then do a freq job to see if the lowest-E stationary point is
really a min.

Errol Lewars
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