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United States Department of Agriculture

Agricultural Research Service

Title: Development of Weiner Et Al. Force Field Parameters Suitable for Conformational Studies of [1,4]-Benzodiazepines and Related Compounds

Authors
item Moyna, Guillermo - TEXAS A&M UNIVERSITY
item Hernandez, Gonzalo - TEXAS A&M UNIVERSITY
item Williams, Howard - TEXAS A&M UNIVERSITY
item Nachman, Ronald
item Scott, A - TEXAS A&M UNIVERSITY

Submitted to: Model and Computer Program Software Documentation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 10, 1997
Publication Date: N/A

Interpretive Summary: One of the problems with the insecticides that are normally used to control pest insects is that insects have the ability over many years to develop what is called resistance to the insecticides. This means that it takes more and more of the insecticide to kill the insect and it can even get to the point that the insecticide is not effective at all. This means that there is always a need to develop new insecticides that can not only get around this resistance phenomenon but that are also safer to the environment. We are doing research on a group of chemicals called neuropeptides, which occur naturally in insects and that serve to regulate a number of necessary life processes such as muscle movement, water balance, digestion, etc. We are trying to find derivatives (called mimetics) of neuropeptides that can be used as insecticides and that will disrupt the normal body functions of pest insects such that they die or cannot reproduce properly. In these studies, we report on the use of sophisticated computer techniques to study the actual shapes of neuropeptide mimetics and how these shapes are necessary for the mimetics to have the biological actions needed to control insects. This work is very important in helping us home in on mimetics that will ultimately be effective in controlling insects and will at the same time be very safe to the environment.

Technical Abstract: A set of AMBER force field parameters capable of reproducing the preferred conformations of the biologically important [1,4]-benzodiazepines was developed. Equilibrium parameters were obtained from representative model compounds found in the Cambridge Structural Database, and bond stretching and torsion potential force constants were estimated using AM1 and PM3 semiempirical Hamiltonians. Parameters obtained with the two semiempirica methods and the existing linear interpolation method are compared. Molecular mechanics and dynamic simulations showed that AM1 derived parameters, together with MNDO ESP fitted atomic charges, predicted the X-ray structure of a number of representative [1,4]benzodiazepines within 0.01 A, 0.8 degrees, and 5 degrees from observed bond lengths, bond angles, and bond torsions respectively.

Last Modified: 7/30/2014
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