I have calculated optimized geometries and energies in water of two diastereomers of one compound. One turned out to be 1.9 kcal/mol more stable than the other (level of theory PBEo-G3bj/6-311g++(d,p)/SMD). There is no sterical hinderance in less stable isomer, and I see no significant difference in its NBO.
The only big difference that I found are the values of dipole moments: more stable isomer - 3.9, less stable - 5.9. The question is how can the difference in dipole moments be used to explain the difference in energy in aqueous solution?