Table 1. Free Energy Difference between the Cis and Trans Isomers (ΔF_c−t), Variation of ΔF_c−t with Respect to Pro (ΔΔF_c−t) and Isomerization Barriers for Proline Dipeptide and Its Analogues in Water^a.

	ΔFc−t, (kcal/mol)	ΔΔFc−t, (kcal/mol)	barrier t → c, (kcal/mol)
Pro	1.1	0.0	15.6
Pip	0.9	−0.2	12.7
Aze	0.4	−0.7	11.7
Dmp	−2.6	−3.7	10.0
Tbp	−2.2	−3.3	10.2
t-4F-Pro	0.6	−0.5	15.6
c-4F-Pro	1.2	0.1	15.6
2-Me-Pro	3.2	2.1	13.8
3-Me-Pro	0.5	−0.6	15.4
2,4-CH2-Pro	2.1	1.0	6.4

^aThe isomerisation barrier is the smallest between the two calculated for clockwise and counterclockwise trans−cis isomerisation.