Computational Chemistry

8. What is parameterization?


9. What advantages does computational chemistry have over “wet chemistry”?


10. Why can’t computational chemistry replace “wet chemistry”?

Harder Questions................................................................

Discuss the following, and justify your conclusions.

1. Was there computational chemistry before electronic computers were
   available?


2. Can “conventional” physical chemistry, such as the study of kinetics, thermo-
   dynamics, spectroscopy and electrochemistry, be regarded as a kind of compu-
   tational chemistry?


3. The properties of a molecule that are most frequently calculated are geometry,
   energy (compared to that of other isomers), and spectra. Why is it more of a
   challenge to calculate “simple” properties like melting point and density?
   Hint: is there a difference between a molecule X and the substance X?


4. Is it surprising that the geometry and energy (compared to that of other
   isomers) of a molecule can often be accurately calculated by a ball-and-springs
   model (molecular mechanics)?


5. What kinds of properties might you expect molecular mechanics to be unable
   to calculate?


6. Should calculations from first principles (ab initio) necessarily be preferred to
   those which make some use of experimental data (semiempirical)?


7. Both experiments and calculations can give wrong answers. Why then should
   experiment have the last word?


8. Consider the docking of a potential drug molecule X into the active site of an
   enzyme: a factor influencing how well X will “hold” is clearly the shape of X;
   can you think of another factor?
   Hint: molecules consist of nuclei and electrons.


9. In recent years the technique ofcombinatorial chemistryhas been used to
   quickly synthesize a variety of related compounds, which are then tested for
   pharmacological activity (S. Borman, Chemical and Engineering News: 2001,
   27 August, p. 49; 2000, 15 May, p. 53; 1999, 8 March, p. 33). What are the
   advantages and disadvantages of this method of finding drug candidates,
   compared with the “rational design” method of studying, with the aid of
   computational chemistry, how a molecule interacts with an enzyme?


10. Think up some unusual molecule which might be investigated computation-
    ally. What is it that makes your molecule unusual?

Harder Questions 7