Photolyases (PHRs) and cryptochromes (CRYs) belong to the same family known as 
blue-light photoreceptors. Although their amino acid sequences and corresponding 
structures are similar to each other, they exert different functions. PHRs 
function as an enzyme to repair UV-induced deoxyribonucleic acid (DNA) lesions 
such as a cyclobutane pyrimidine dimer (CPD) and a (6-4) photoproduct ((6-4)pp), 
whereas CRYs are a circadian photoreceptor in plants and animals and at the same 
time they control the photoperiodic induction of flowering in plants. When a new 
type cryptochrome was identified, it was assumed that another type of CRYs, 
cryptochrome-DASH (CRY-DASH), which is categorized as a subfamily of 
photolyase/cryptochrome family, would possess the DNA photolyase activity. 
However, CRY-DASH had a weak DNA photolyase activity, but the reason for this is 
still unclear. To clarify the reason, we performed molecular dynamics (MD) 
simulations for a complex of CPD-PHR or CRY-DASH with damaged double-stranded 
DNA (dsDNA) and estimated the binding free energy, ΔGbind, between the protein 
and the damaged dsDNA by using a molecular mechanics/Poisson-Boltzmann surface 
area (MM/PBSA) method. ΔGbind for both proteins were -35 and 57 kcal mol-1, 
respectively, indicating that the structural stability of CRY-DASH was lower 
than that of CPD-PHR upon the damaged dsDNA binding. In particular, the number 
of amino acid residues relevant to the damaged dsDNA binding on the CRY-DASH 
surface was smaller than that on CPD-PHR. Therefore, the present result suggests 
that CRY-DASH has a weak DNA photolyase activity because it has a lower binding 
affinity than CPD-PHR.