Subject: Summary:Definition of molecular flexibility

From: Bruno Bienfait <[email-masked]>
Date: Fri, 10 Oct 1997 17:04:55 -0400

10 days ago, I posted this question to the CCL:
"I am looking for a definition of molecular flexibility. Does anyone
know
a paper or a book which defines this concept ? Furthermore, are
molecular flexibility and conformational flexibility the same concept ?"

Here follow the 8 responses I received:

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        For a quantification of molecular flexibility, see QSAR:
Quantitative
Structure-Activity Relationships in Druig Design, Alan R. Liss, Inc.,
1989,
pp. 105-109.

S. Shapiro
[email-masked]

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A keyword to look for may be:

                      persistence length

But I'm not familiar with this, so I can't give you any good
reference.  But this concept was recently used by Cheatham (J. Mol.
Biol. 259, 434-444, 1996) to analyse DNA flexibility in a molecular
dynamics run.

Peter Slickers                                [email-masked]

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Clark, D.E., Willett, P. and Kenny, P.W.
Pharmacophoric Pattern Matching in Files of Three-Dimensional Chemical
Structures:
Implementation of Flexible Searching.
Journal of Molecular Graphics 11. 146-156, 1993.

We compared 4 different measures of molecular flexibility.

Best regards
David 
        [email-masked]

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We have tried to do some work in the area. Just  a few references of our
papers. The key papers are the last two references.

Kriz Z, Koca J, Carlsen~P.H.J.: {\it Conformational behavior and
flexibility of terminally blocked cysteine and cystine}. J.~Mol.~Mod.
{\bf 2}, 51-61 (1996).

Koca J., Carlsen P.H.J.: {\it Conformational Behavior and Flexibility
of Met-enkephalin}. J.~Mol. Struct. (Theochem) {\bf 337}, 17-24 (1995).  

Koca J., Perez S., Imberty A.: {\it Conformational Analysis and 
Flexibility of Carbohydrates using the CICADA approach with MM3.}
J. Comput. Chem. {\bf 16}, 296-310 (1995).

!!!!!!!!!!!!!!!!!!!
!!!  Koca J.: {\it Potential Energy Hypersurface and Molecular
Flexibility.}
 J. Mol. Struct.~{\bf 291}, 255-269~(1993). !!!!!!
!!!!!!!!!!!!!!!!!!!

!!! Koca J., Carlsen P.H.J.: {\it DAISY, A Computational Method.
A Novel Tool for a Study of Conformational Behavior of Flexible
Molecules}.
J.~Mol. Struct.~(Theochem)~{\bf 257}, 105-130 (1992).

Jaroslav Koca

 www: http://web.chemi.muni.cz/~jkoca; 
e-mail: [email-masked] 
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Polymer science uses several rigidity metrics for linear macromolecules. 
(e.g. Coon's segment (spelling probably wrong since I only saw it in 
Russian)). You might want to consult a basic book on polymer science.

Regards,
Eugene

        Eugene Leitl <[email-masked]>

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In response to your recent request for a definition of molecular 
flexibilty we would like to make the following comments.

We cannot provide you with a reference to a paper or a book 
containing a formal definition of "molecular flexibility", but in our 
own work on the molecular modelling of metal-ligand complex species, 
we have found it useful to view conformational flexibility as one of 
the components of molecular flexibility.

Viewed in terms of the multi-dimensional potential/steric energy (PE) 
surface of a molecule involved in molecular mechanics, each minimum 
in the surface corresponds to a conformation. The conformational 
flexibility might be quantified as proportional to the number of 
minima in that surface which are of reasonably low energy. This 
includes the global minimum and all the other local minima of 
reasonably low energy. A Boltzman weighting factor could be used to 
weight the relative contributions of the various minima found. The 
set of potential energy minima could, in principle, be found by a 
technique like quenched dynamics.

Another contribution to molecular flexibility is the flexibility of a 
particular conformation of a molecule towards an applied distorting 
force. An example would be the response of a macrocyclic ligand (or 
indeed any ligand system) in a metal-ligand complex to change in the 
size of a metal ion. This can be quantified as the curvature (or 
second derivative) of the section through the PE surface 
corresponding to change in the metal ion size, at the PE minimum. 
This we have termed the "stiffness" of a conformation.

We feel therefore that there are at least two contributions to 
molecular flexibility. One of them is related to the number of 
accessible minima in the PE surface, and the other to the curvature 
of the minima in that surface.

There may, of course, be yet other contributions to consider.

We hope this reply is helpful.

We are interested in any debate that may ensue on CCL on this 
subject, so we would be most obliged if you would kindly post a 
summary of responses on CCL in due course.

Kind regards,

GARY PATTRICK, ROBERT D. HANCOCK, & FABRI MARSICANO
"Fabri Marsicano" <[email-masked]>

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Thanks to all who replied.

Bruno

-- 
[ Bruno Bienfait, Ph. D.            Laboratory of Medicinal Chemistry ]
[                                   National Cancer Institute         ]
[ Email : [email-masked]      National Institutes of Health     ]
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