Subject: Re: CCL:Compendium of bound conformations

From: Per-Ola Norrby <[email-masked]>
Date: Wed, 17 Mar 1999 11:16:51 +0100

>Dear Colleagues;
>
>	I am seekings articles/reviews documenting differences between
>experimentally-determined (or experimentally-inferred) conformations of
>"small" (i.e. non-macromolecular) substrates/ligands and their in vacuo
>counterparts calculated using molecular or quantum mechanics.  If anyone
>has relevant citations, I'd appreciate your sharing those citations with me.
>
>Thanks in advance to all responders,
>
>S. Shapiro
>[email-masked]

	Dear Dr. Shapiro,

	Please see our recent article "Conformational energy penalties of
protein-bound ligands", by J. Boström, P.-O. Norrby, and T. Liljefors in
J.Comp.-Aid.Mol.Design 12, 383 (1998).  Also relevant are some earlier
studies referenced therein, in particular Nicklaus et al, Bioorg.Med.Chem.
3, 411 (1995).  In short, the results are that in vacuo structures can be
substantially different from bound conformations.  The correct comparison
is with the solution ensemble, not with gas phase data.  In most cases, if
you compare inner energies of bound ligands to the inner energy of solvated
ligands, the differences are below 3 kcal/mol.  Most of the exceptions can
be traced to imperfections in the force fields or to errors in the
experimentally determined bound structure.

	Best regards,

	Per-Ola Norrby

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
 *  Per-Ola Norrby, Associate Professor
 *  The Royal Danish School of Pharmacy, Dept. of Med. Chem.
 *  Universitetsparken 2, DK 2100 Copenhagen, Denmark
 *  tel. +45-35376777-506, +45-35370850    fax +45-35372209
 *  Internet: [email-masked], http://compchem.dfh.dk/PeO/