We report quantum mechanical computations and experimental evidence which suggest that the backbone conformation of globular proteins depends generally on the conservation of that part of the hydrogen bond network or ribbon which is joined, in general, directly to the backbone and is largely independent of the remainder of this whole network of hydrogen bonds. The familiar hydrogen bonds of the
helix and the
sheet form about one-half of this ribbon of hydrogen bonds. Both water molecules and hydrogen bonding side chain groups are involved in the formation of the ribbon.This view of the three-dimensional structure of globular proteins in terms of the `molecule'' allows us to deal with the non-secondary structure as well as with the familiar secondary structure. It also suggests that the ribbon contains approximately the same number of hydrogen bonds within all three structures – the
helix, the
sheet and the coil – and that this is the reason for the ease of interconversion of these three structures.
The quantum mechanical computations on hydrogen bonding suggest that delocalised water molecules which have substantial mobility are an essential part of the ribbon. This situation arises because the hydrogen bonding groups of the protein molecule are not free to move to optimise the hydrogen bonding geometries as are the oxygen atoms in the waters and ices. Such delocalised water molecules either have high B values or are invisible in the X-ray data and yet are able to form a structure which is as strong as a normal hydrogen bond.
The experimental data on the point mutations of the THRI57 residue of the T4 phage lysome provides an initial test of this model. Both the local backbone conformation and the ribbon of hydrogen bonds are conserved throughout all the mutations of residue 157,providing that the delocalised water molecules are accepted as a genuine part of the structure. These mutations include the introduction of hydrocarbon side chains at position 157 when water molecules or other side chain groups take over the formation of the hydrogen bonds.
We suggest that, provided steric effects are not important, many point mutations succeed because they leave the ribbon of hydrogen bonds (and so the backbone conformation) largely unchanged.
Coil structure - energetics - hydrogen conformations bonding - protein - quantum mechanical theory