Enantioselectivity and Enzyme-Substrate Docking Studies of a Ketoreductase from Sporobolomyces salmonicolor (SSCR) and Saccharomyces cerevisiae (YOL151w)
Table 1
Aryl ketones (ArK).
ID name
Compound name
R1
R2
(kcal/mol)
(kcal/mol)
ee (%)
Prelog
Prediction correct
ArK1*
Acetophenone
H
CH3
−39.9
−37.8
42 (R)
Anti
Y
ArK2*
Propiophenone
H
CH2CH3
−40.6
−38.1
28 (R)
Anti
Y
ArK3*
1-Phenylbutan-1-one
H
(CH2)2CH3
−44.2
−44.4
88 (S)
Prelog
Y
ArK4*
1-Phenylpentan-1-one
H
(CH2)3CH3
−45.5
−47.3
87 (S)
Prelog
Y
ArK5*
1-Phenylhexan-1-one
H
(CH2)4CH3
−47.0
−50.7
34 (S)
Anti
Y
ArK6*
1-Phenylheptan-1-one
H
(CH2)5CH3
−49.7
−53.1
27 (S)
Anti
Y
ArK7*
2-Methyl-1-phenylpropan-1-one
H
CH(CH3)2
−44.4
−41.5
98 (R)
Anti
Y
ArK8*
2,2-Dimethyl-1-phenylpropan-1-one
H
C(CH3)3
−47.6
NS
98 (R)
Anti
Y
ArK9†
2-Chloro-1-phenylethanone
H
CH2Cl
−39.9
−45.3
98 (S)
Anti
Y
ArK10*
Cyclopropyl(phenyl)methanone
H
cyclo-C3H5
−46.2
−41.5
96 (R)
Anti
Y
ArK11*
Cyclopropyl(4-fluorophenyl)methanone
4′-F
cyclo-C3H5
−49.8
NS
98 (R)
Anti
Y
ArK12*
4-Chlorophenyl(cyclopropyl)methanone
4′-Cl
cyclo-C3H5
−52.2
−33.7
98 (R)
Anti
Y
ArK13†
1-(4-Fluorophenyl)ethanone
4′-F
CH3
−40.4
−36.2
46 (R)
Anti
Y
ArK14†
1-(4-Chlorophenyl)ethanone
4′-Cl
CH3
−44.7
NS
14 (R)
Anti
Y
ArK15†
1-(4-Bromophenyl)ethanone
4′-Br
CH3
−44.6
NS
42 (R)
Anti
Y
ArK16†
1-p-Tolylethanone
4′-CH3
CH3
−42.7
NS
59 (R)
Anti
Y
ArK17†
1-(4-Methoxyphenyl)ethanone
4′-OCH3
CH3
−42.9
NS
57 (R)
Anti
Y
ArK18†
1-(4-(Trifluoromethyl)phenyl)ethanone
4′-CF3
CH3
−46.7
NS
17 (S)
Prelog
N
ArK19†
1-(2-chlorophenyl)ethanone
2′-Cl
CH3
−42.6
−37.6
15 (R)
Anti
Y
ArK20†
1-o-Tolylethanone
2′-CH3
CH3
−43.3
−41.3
70 (R)
Anti
Y
ArK21†
1-(2-Methoxyphenyl)ethanone
2′-OCH3
CH3
−49.6
−49.5
99 (R)
Anti
Y
ArK22†
1-(3-Chlorophenyl)ethanone
3′-Cl
CH3
−40.5
−40.8
66 (R)
Anti
N
ArK23†
1-m-Tolylethanone
3′-CH3
CH3
−42.3
NS
92 (R)
Anti
Y
ArK24†
1-(3,5-Bis(trifluoromethyl)phenyl)ethanone
3′,5′-(CF3)2
CH3
−45.2
NS
99 (R)
Anti
Y
ArK25†
1-Tetralone
−42.4
−37.7
94 (R)
Prelog
Y
ArK26†
6-Methyl-4-chromanone
−46.2
−45.7
99 (R)
Prelog
Y
NS = no structure found meeting the requirements. and refer to the lowest energy docking pose that meets the criteria for valid structure whose geometry is pro or , respectively. Literature values for the enantiomeric excess (ee (%)) were obtained as follows: *values are from [11], and †values are from [9]. Prelog column indicates if the enzyme followed prelog or antiprelog rule for the given substrate. The last column indicates if the model correctly predicted the experimental results.
