Computational binding energetics

Table 2.46 Binding energetics of complexes of amide with water or another amide (see Fig. 2.23 for definitions). All data computed with aug-cc-pVDZ basis set and corrected for BSSE, in kcal/moF .

The energetics, too, illustrate the cooperative nature of the two H-bonds. As reported in Table 2.48, the formamide and formic acid molecules are bound together in the cyclic complex by some 12.6 kcal/mol at the MP2/DZP level. The (OH--0) H-bond of structure (b) contributes 7.0 kcal/mol while 3.8 kcal/mol more arises from the (NH"0) interaction. Together, these two separate H-bonds add up to less than the full interaction in the cyclic structure. (Structures (b) and (c) do not represent true minima on the potential energy surface.) It is interesting to note that correlation plays little apparent role in the computed binding energies of this particular complex. 

Enzyme-substrate interactions. While TS analysis can provide a detailed TS structure, and it is possible to dock that stmcture into an enzyme active site, it is not possible to determine by inspection or computation the energetics of individual enzyme-substrate contacts. An added complication is the fact that active sites generally change structure upon binding to the transition state and throughout the catalytic cycle. Further experimental studies, in combination with computational analyses of enzyme-substrate interactions are needed to understand the energetics of catalysis. 

D P f Goodford 1985. A Computational Procedure for Determining Energetically Favorable Binding Sites on Biologically Important Macromolecules. Journal of Medicinal Chemistry 28 849-857. Molecular Discovery Ltd, Oxford, United Kingdom. 

PI Goodford. A computational procedure for determining energetically favorable binding sites on biologically important macromolecules. I Med Chem 28 849-957, 1985. 

We have shown that a tight-binding scheme accounts for many physical phenomena which are of importance for the understanding of the energetics of surface defects and of crystal growth. This method which is simple and much less computer time demanding than ab initio methods is thus very useful to derive trends along the transition series. 

---