Subject: Conforamation composition

From: yunlong song <[email-masked]>
Date: Tue, 18 Jul 2000 14:18:28 +0800

Dear computational chemists,
I am performing conformational analysis on a drug molecule.I want to know the exact population of each conformer.
I want to know how to calculation the conformation population analysis based on Boltzmann law? Can you help me ?
Also, I want to know how to calculate torsion energy profile according a torsion bond.The interal coordinates may be
useful,however the molecule is quite large.I use its cartesian coordinate.So can I use cartesian coordinate to comput 
the pofile. In literature, people often referred to reaction coordinate drive method.Can someone give me an exact explanation?

Thanks in advance!

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From: Rick Venable <[email-masked]>
Date: Mon, 17 Jul 2000 12:14:15 -0700

On Tue, 18 Jul 2000, yunlong song wrote:
> I am performing conformational analysis on a drug molecule.I want to
> know the exact population of each conformer. I want to know how to
> calculation the conformation population analysis based on Boltzmann
> law? Can you help me ? 

Monte Carlo simulations use Boltzmann based sampling to build up a
family of conformations with a Boltmann energy distribution.  
Typically, these calcs use rotation around single bonds as the free
variables, especially for smaller molecules like drugs.  Because the
calcs are usually run in a vacuum environment, the distribution
represents the gas phase of the molecule.

> Also, I want to know how to calculate torsion energy profile
> according a torsion bond.The interal coordinates may be
> useful,however the molecule is quite large.I use its cartesian
> coordinate.So can I use cartesian coordinate to comput the pofile.
> In literature, people often referred to reaction coordinate drive
> method.Can someone give me an exact explanation?

Both sampling of a single torsion and Monte Carlo sampling are best done
using internal coordinates for generating configurations.  Many progs
require Cartesian coords to evaluate energy, and so must use perturbed
internal coords to compute the Cartesian coords, and then the energy.

Reaction coordinate usually refers to some movement (rotation,
translation) used to study an energy profile, and typically represents a
simplification to a single movement with the assumption that other parts
of the system remain in some fixed geometry.  For a drug molecule with
multiple freely rotating single bonds, this can be a problem; the energy
profile for one single bond torsion may depend on the conformational
state of other single bonds in the molecule.

--
Rick Venable                  =====\     |=|    "Eschew Obfuscation"
FDA/CBER Biophysics Lab       |____/     |=|
Bethesda, MD  U.S.A.          |   \    / |=|  ( Not an official statement or
[email-masked]          |    \  /  |=|    position of the FDA; for that,
[email-masked]              \/   |=|    see   http://www.fda.gov  )