Re: CCL:Conforamation composition

[Rick Venable <rvenable at.at gandalf.cber.nih.gov>]

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
 Rick_Venable at.at nih.gov          |    \  /  |=|    position of the FDA; for
 that,
 rvenable at.at speakeasy.org              \/   |=|    see   http://www.fda.gov  )