From Protein Structure to Function with Bioinformatics.pdf

7 Predicting Protein Function from Surface Properties 179therefore direct computational approaches towards the most energetically importantsurface points. Energetic approaches for doing this were pioneered by PeterGoodford and his widely used program GRID (Goodford 1985). In this case, as inother methods that followed, the interaction of the protein with a probe atom at a3D grid point on the protein surface is modelled by the protein-probe interactionenergy i.e. the van der Waals, hydrogen-bonding and electrostatic contributions.This reflects the ability of the probe to interact favourably with the protein at thatpoint. Particularly favourable points of interaction can be retained for visualisation(Fig. 7.5), and may aid in the design of new ligands. Another similar approach is touse a knowledge-based potential. For example, SuperStar (Nissink et al. 2000), isderived from the statistical analysis of a large number of protein-ligand interactionsobserved in the structural database. Either application can help to annotate a potentialbinding site, defining regions where possible interactions between chemicalgroups are preferable.Fig. 7.5 Q-fit (Jackson, 2002) grid map, for the binding site of periplasmic binding protein (PDBcode: 2GBP), showing the most favourable grid interaction points for the hydroxyl oxygen probe(white). The bound ligand glucose (not present in the calculation) is shown for reference. It canbe seen that four of the five hydroxyl groups of glucose are picked out well by the most favourableprobe positions