Biomedical Engineering Reference
In-Depth Information
HETATM 9 C
9
4.694
1.557
−
0.049
HETATM 10 N
10
3.025
1.002
1.616
etc.etc.
CONECT 12613
CONECT 21314
CONECT 32415
CONECT 4
3
5
7
etc. etc.
END
Records 1 through 23 identify the atoms; so, for example, atom1 is a carbon. The 'CONECT
1 2 6 13' record tells us that atom 1 (C) is joined to atoms 2, 6 and 13.
6.4 QSAR
Quantitative structure-activity relationships (QSARs) are attempts to correlate molecular
structure with chemical or biochemical activity. I will use the remainder of this chapter
to give you a flavour for the QSAR properties that are often routinely calculated in MM
studies.
6.4.1 Atomic Partial Charges
Atomic charges can be calculated using the (costly) techniques of molecular quantum
mechanics, as wewill discover in later chapters. They are often calculatedwithin the spirit of
QSAR analyses using the partial equalization of orbital electronegativity (PEOE) approach
of Gasteiger and Marsili (1980). The key concept of their method is atom
electronegativity
(often given the symbol χ ), and an attraction is that their calculation is rapid. Pauling and
Yost (1932) first introduced this concept, and they tried to give numerical values to atomic
electronegativities based on bond energy values. Mulliken (1934) put the concept on a
firmer theoretical footing by relating an atomic electronegativity to the ionization energy
I
and the electron affinity
E
of the atom concerned:
1
2
(
I
χ
=
+
E
)
(6.1)
The only problemwithMulliken's definition is that both
E
and
I
relate to somemythical state
of an atom called the
valence state
. There have been many learned discussions relating to
the concept of valence state, and such discussions still occasionally appear in the literature.
Whatever the valence state of an atom is (depending on the atom), it rarely corresponds
to a spectroscopic state and so cannot be studied experimentally. Electronegativities and
valence states go hand in hand; they are part of our folklore and both are widely quoted in
even the most elementary chemistry texts.
Sanderson (1951) proposed that, on bond formation, atoms change their electron density
until their electronegativities are equal. These ideas were further elaborated by Hinze and
co-workers (1963), who introduced the concept of
orbital electronegativity
. This is the
