Molecular mechanics hydrogen bonding potentials

A hydrogen-bond potential which is parameterized for use with a particular molecular mechanics program will not be transferable to another molecular mech-... 

Vedani A, Dunitz JD (1985) Lone-pair directionality in hydrogen bond potential functions for molecular mechanics calculations. The inhibition of human carbonic anhydrase II by sulfonamides. J Am Chem Soc 107 7653-7658... 

A. Vedani and J. D. Dunitz,/. Am. Chem. Soc., 107, 7653 (1985). Lone-Pair Directionality in Hydrogen Bond Potential Functions for Molecular Mechanics Calculations The Inhibition of Human Carbonic Anhydra.se II by Sulfonamides. 

Diels-Alder reactionsJ Using a combined quantum-mechanical and molecular-mechanical (QM/MM) potential, Gao carried out Monte Carlo simulations to investigate the hydrophobic and hydrogenbonding effects on Diels-Alder reactions in aqueous solution. Enhanced hydrogen-bonding interaction and the hydrophobic effect were found to contribute to the transition-state stabilization. The number of hydrogen bonds was found to cause strong Coulomb interaction and discriminate heats of formation of transition states for exo/endo products. 

Using molecular mechanics calculations to assess the three-dimensional shape of a molecule, various surface properties such as polarity and size can be calculated. The dynamic molecular surface properties can be determined from the (low energy) conformation(s) of the drug molecule obtained by molecular mechanics calculations of conformational preferences. The potential advantage of this method is that the calculated surface character-sitics determine numerous physicochemical properties of the molecules including lipophilicity, the energy of hydration and the hydrogen bond formation capacity [187-... 

The three prototype mixed p agonist/S antagonists described in this chapter have excellent potential as analgesics with low propensity to produce tolerance and dependence. The pseudotetrapeptide DIPP-NH2[ ] has already been shown to produce a potent analgesic effect, less tolerance than morphine, and no physical dependence upon chronic administration. In preliminary experiments, the tetrapeptides DIPP-NH2 and DIPP-NH2[T] were shown to cross the BBB to some extent, but further structural modifications need to be performed in order to improve the BBB penetration of these compounds. The Tyr-Tic dipeptide derivatives can also be expected to penetrate into the central nervous system because they are relatively small, lipophilic molecules. In this context, it is of interest to point out that the structurally related dipeptide H-Dmt-D-Ala-NH-(CH2)3-Ph (SC-39566), a plain p-opioid agonist, produced antinociception in the rat by subcutaneous and oral administration [72], As indicated by the results of the NMR and molecular mechanics studies, the conformation of the cyclic p-casomorphin analogue H-Tyr-c[-D-Orn-2-Nal-D-Pro-Gly-] is stabilized by intramolecular hydrogen bonds. There-... 

The various types of successful approaches can be classified into two groups empirical model calculations based on molecular force fields and quantum mechanical approximations. In the first class of methods experimental data are used to evaluate the parameters which appear in the model. The shape of the potential surfaces in turn is described by expressions which were found to be appropriate by semiclassicala> or quantum mechanical methods. Most calculations of this type are based upon the electrostatic model. Another more general approach, the "consistent force field method, was recently applied to the forces in hydrogen-bonded crystals 48> 49>. 

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