Interaction energy, negative, favorable

As you might expect, the favored orientation of a polar molecule in the presence of ions is one where the positive end of the dipole is near an anion and the negative end of the dipole is near a cation. The magnitude of the interaction energy E depends on the charge on the ion z, on the strength of the dipole as measured by its dipole moment /x, and on the inverse square of the distance r from the ion to the dipole E = z/x/r2. Ion-dipole forces are particularly important in aqueous solutions of ionic substances such as NaCl, in which polar water molecules surround the ions. We ll explore this point in more detail in the next chapter. 

This functional is also physically motivated as it expresses the balance of two terms a favorable (negative) solute-solvent interaction energy and an unfavorable (positive) solvent-solvent interaction. At equilibrium the second term is equal to half of the first as expected also from basic electrostatic arguments. 

Usually, any positive interaction energy present in the X matrix is then set to 0 kcal mol Thus one focuses on the negative, favorable interaction energies and removes the information about small protein shape differences. Additionally, only using negative interaction energies allows a straightforward interpretation of the results. 

It is usually energetically unfavorable for a molecule to act as a double proton acceptor as BH would in Fig. 5.1. For similar reasons, cooperativity is typically negative also when a molecule acts as double proton donor. Of course, even in the case of negative cooperativity, formation of the second H-bond is usually energetically favorable when compared to the complete absence of a second H-bond. That is, even though the CH -BH interaction above is weaker than it would be in the absence of the other proton donor, AH, this interaction energy is still negative, and so wiU form spontaneously. In other words, two H-bonds are always better than one (or usually so). 

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