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3.3 MHC-Peptide Interaction Parameters
The forces involved in protein-protein interactions are non-covalent and therefore
reversible, and are generally effective over short distances. These include: (i) van der
Waals (attractive and repulsive) interaction, (ii) electrostatic interactions (including
hydrogen bonds), and (iii) hydrophobic interactions. It is a balance of these
interactions against interactions with solvent that determines the stability of a
protein. Some interaction parameters have been identified as being significant for the
characterization of pMHC interface (Kangueane, Sakharkar, Kolatkar, and Ren
2001; Tong, Kong, Tan, and Ranganathan 2006) and can be calculated from the
three-dimensional coordinates of a complex.
3.3.1 Interface Area between Peptide and MHC
The hydrophobic effect is considered to be one of the most significant forces that
drive protein folding. A linear correlation exists between the hydrophobic free
energy of transfer from polar to hydrophobic environment and the change in solvent
accessible surface area (ΔASA) upon complexation (Chothia and Janin 1975). Thus,
knowledge of the surface area of a complex interface in direct contact with solvent
may provide an indication of the binding strength. The accessible surface area can be
measured by tracing out the maximum permitted van der Waals contact that is
covered by the center of a water molecule as it rolls over the surface of the protein.
Interface area for class I pMHC complexes was defined as the mean ΔASA on
complexation when going from a monomeric MHC molecule to a dimeric pMHC
complex state and calculated as half the sum of the total ΔASA for both molecules
for each type of complex. The mean ΔASA for class I pMHC complexes is 903.30 ±
260.90 Å
2
. Similarly, the interface area for class II pMHC complexes was defined as
the ΔASA when going from a dimeric MHC molecule to a trimeric state. The
corresponding ΔASA in class II complexes is 894.40 ± 364.00 Å
2
.
3.3.2 Intermolecular Hydrogen Bonds
Hydrogen bonds are major contributors to the selectivity and stability of protein-
protein complexes. It involves three atoms, a donor electronegative atom to which
the hydrogen is bound, and an acceptor electronegative atom in close proximity.
The typical observed hydrogen bond distance is approximately 2.60 to 3.10 Å
(1.00 to 1.20 Å between donor and hydrogen and 1.60 to 2.00 Å between acceptor
and hydrogen). For such bonding to be significant, both electronegative atoms
must be derived from the group: F, N, and O (Morrison and Boyd 1992). Only
hydrogen bonded to any of these three elements is sufficiently positive, and only
these elements are sufficiently negative for the required attraction to exist due to
the high concentration of negative charge on their small atoms. Hydrogen bonds
are directional and can control and restrict the geometry of the interactions
between side-chains. In general, the strength of hydrogen bonds increases with
decreasing bond length.
