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Molecular Mechanics

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Abstract

Molecular mechanics (MM) rests on a view of molecules as balls held together by springs. The potential energy of a molecule can be written as the sum of terms involving bond stretching, angle bending, dihedral angles and nonbonded interactions. Giving these terms explicit mathematical forms constitutes devising a forcefield, and giving actual numbers to the constants in the forcefield constitutes parameterizing the field. An example is given of the devising and parameterization of an MM forcefield. Calculations on biomolecules is a very important application of MM, and the pharmaceutical industry designs new drugs with the aid of MM. Organic synthesis now makes considerable use of MM, which enables chemists to estimate which products are likely to be favored and to devise more realistic routes to a target molecule. In molecular dynamics MM is used to generate the forces acting on molecules and hence to calculate their motions.

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Notes

  1. 1.

    Frank H. Westheimer, born Baltimore, Maryland, 1912. Ph.D. Harvard 1935. Professor University of Chicago, Harvard. Died 2007.

  2. 2.

    Edward D. Hughes, born Wales, 1906. Ph.D. University of Wales, D.Sc. University of London. Professor, London. Died 1963.

  3. 3.

    Christopher K. Ingold, born London 1893. D.Sc. London 1921. Professor Leeds, London. Knighted 1958. Died London 1970.

  4. 4.

    Paul von R. Schleyer, born Cleveland, Ohio, 1930. Ph.D. Harvard 1957. Professor Princeton; institute codirector and professor University of Erlangen-Nürnberg, 1976–1998. Professor University of Georgia.

  5. 5.

    Norman L. Allinger, born Rochester New York, 1930. Ph.D. University of California at Los Angeles, 1954. Professor Wayne State University, University of Georgia.

References

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  10. To properly parameterize a molecular mechanics forcefield by calculations only high-level ab initio (or density functional) calculations would actually be used, but this does not affect the principle being demonstrated

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  11. Reference 1b, section 4.8

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Authors and Affiliations

  1. Dept. Chemistry, Trent University, West Bank Drive 1600, K9J 7B8, Peterborough, Ontario, Canada

    Prof. Errol G. Lewars

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Correspondence to Errol G. Lewars .

Appendices

Easier Questions

  1. 1.

    What is the basic idea behind molecular mechanics?

  2. 2.

    What is a forcefield?

  3. 3.

    What are the two basic approaches to parameterizing a forcefield?

  4. 4.

    Why does parameterizing a forcefield for transition states present special problems?

  5. 5.

    What is the main advantage of MM, generally speaking, over the other methods of calculating molecular geometries and relative energies?

  6. 6.

    Why is it not valid in all cases to obtain the relative energies of isomers by comparing their MM strain energies?

  7. 7.

    What class of problems cannot be dealt with by MM?

  8. 8.

    Give four applications for MM. Which is the most widely used?

  9. 9.

    MM can calculate the values (cm−1) of vibrational frequencies, but without “outside assistance” it can’t calculate their intensities. Explain.

  10. 10.

    Why is it not valid to calculate a geometry by some slower (e.g. ab initio) method, then use that geometry for a fast MM frequency calculation?

Harder Questions

  1. 1.

    One big advantage of molecular mechanics over other methods of calculating geometries and relative energies is speed. Does it seem likely that continued increases in computer speed could make MM obsolete?

  2. 2.

    Do you think it is possible (in practical terms? In principle?) to develop a forcefield that would accurately calculate the geometry of any kind of molecule?

  3. 3.

    What advantages or disadvantages are there to parameterizing a forcefield with the results of “high-level” calculations rather than the results of experiments?

  4. 4.

    Would you dispute the suggestion that no matter how accurate a set of MM results might be, they cannot provide insight into the factors affecting a chemical problem, because the “ball and springs” model is unphysical?

  5. 5.

    Would you agree that hydrogen bonds (e.g. the attraction between two water molecules) might be modelled in MM as weak covalent bonds, as strong van der Waals or dispersion forces, or as electrostatic attractions? Is any one of these three approaches to be preferred in principle?

  6. 6.

    Replacing small groups by “pseudoatoms” in a forcefield (e.g. CH3 by an “atom” about as big) obviously speeds up calculations. What disadvantages might accompany this simplification?

  7. 7.

    Why might the development of an accurate and versatile forcefield for inorganic molecules be more of a challenge than for organic molecules?

  8. 8.

    What factor(s) might cause an electronic structure calculation (e.g. ab initio or DFT) to give geometries or relative energies very different from those obtained from MM?

  9. 9.

    Compile a list of molecular characteristics/properties that cannot be calculated purely by MM.

  10. 10.

    How many parameters do you think a reasonable forcefield would need to minimize the geometry of 1,2-dichloroethane?

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Lewars, E.G. (2011). Molecular Mechanics. In: Computational Chemistry. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3862-3_3

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