1. An optical pickup for recording andor reproducing data with respect to a multilayer recording medium having a plurality of recording layers, the optical pickup comprising:
a light source emitting a beam having a predetermined wavelength;
a diffraction unit separating the beam emitted from the light source into a main beam and a sub-beam; and
a photo-detector having a main photodetector, detecting the main beam reflected from the multilayer recording medium, and a sub-photodetector detecting the sub-beam,
wherein the main photodetector and the sub-photodetector are separated a predetermined distance Ds from each other so that a beam spot formed by the beam reflected from a defocus recording layer of the multilayer recording medium is not detected by the sub-photodetector, and
wherein the predetermined distance Ds between the main photodetector and the sub-photodetector satisfies the following inequality:
Ds\u2267A2+QR
wherein \u201cR\u201d is a radius of the beam spot formed by the beam reflected from the defocus recording layer, \u201cA\u201d is a width of the sub-photodetector, and \u201cQ\u201d is a coefficient indicating an allowable range of a DC offset of a sub-push-pull signal, and
wherein the coefficient Q is between 0.85-0.90 when the allowable range of the DC offset is not more than 5%.
2. The optical pickup as claimed in claim 1, wherein the radius R satisfies the following equation:
R
=
2
\xd7
d
sp
n
sp
\xd7
M
\xd7
NA
,
wherein, \u201cdsp\u201d is a thickness of a spacer layer between the defocus recording layer and a recording layer that is subject to recording andor reproduction, \u201cnsp\u201d is a refractive index of the spacer layer, \u201cM\u201d is a magnifying power of the optical pickup, and \u201cNA\u201d is a numerical aperture of an objective lens used in the optical pickup.
3. The optical pickup as claimed in claim 1, wherein the main photodetector is a four-section photodetector.
4. The optical pickup as claimed in claim 1, wherein the sub-photodetector is a two-section photodetector.
5. The optical pickup as claimed in claim 1, further comprising a calculation portion calculating signals detected by the main photodetector and the sub-photodetector and outputting a differential push-pull signal.
6. A method of setting an optical pickup including a light source emitting a beam having a predetermined wavelength, a diffraction unit separating the beam emitted from the light source into a main beam and a sub-beam, and a photodetector having a main photodetector, detecting the main beam reflected from a multilayer recording medium, and a sub-photodetector detecting the sub-beam, the method comprising:
setting a distance Ds between the main photodetector and the sub-photodetector to satisfy the following inequality, to prevent a beam spot formed by the main beam from being detected by the sub-photodetector:
D
s
\u2265
A
2
+
QR
,
wherein \u201cR\u201d is a radius of the beam spot formed by the beam reflected from a defocus recording layer, \u201cA\u201d is a width of the sub-photodetector, and \u201cQ\u201d is a coefficient indicating an allowable range of a DC offset of a sub-push-pull signal, and
wherein the coefficient Q is between 0.85-0.90 when the allowable range of the DC offset is not more than 5%.
7. The method as claimed in claim 6, wherein the radius R satisfies the following equation:
R
=
2
\xd7
d
sp
n
sp
\xd7
M
\xd7
NA
,
wherein, \u201cdsp\u201d is a thickness of a spacer layer between the defocus recording layer and a recording layer that is subject to recording andor reproduction, \u201cnsp\u201d is a refractive index of the spacer layer, \u201cM\u201d is a magnifying power of the optical pickup, and \u201cNA\u201d is a numerical aperture of an objective lens used in the optical pickup.
8. An optical pickup for use with a multilayer recording medium having a plurality of recording layers that are subject to recording andor reproduction, the optical pickup comprising:
a photodetector having a main photodetector and a sub-photodetector, wherein, when a distance between the main photodetector and the sub-photodetector is Ds, the distance Ds satisfies the following inequality:
d
sp
\u2264
(
D
s
–
A
2
)
\xd7
n
sp
2
\u2062
Q
\xd7
M
\xd7
NA
,
wherein \u201cA\u201d is a width of the sub-photodetector, \u201cQ\u201d is a coefficient indicating an allowable range of a DC offset of a sub-push-pull signal, \u201cnsp\u201d is a refractive index of a spacer layer between the plurality of recording layers, \u201cM\u201d is a magnifying power of the optical pickup, and \u201cNA\u201d is a numerical aperture of an objective lens used for the optical pickup.
9. The optical pickup as claimed in claim 8, wherein the coefficient Q is between 0.85-0.90 when the allowable range of the DC offset is not more than 5%.
10. The optical pickup as claimed in claim 8, wherein the optical pickup performs a tracking servo control using a differential push-pull method.
11. The optical pickup as claimed in claim 9, wherein the coefficient indicating the allowable range of the DC offset is determined based on the range of the DC offset of the sub-push-pull signal.
12. The optical pickup as claimed in claim 1, wherein the light source is configured to emit a beam in a blue wavelength range.
13. The optical pickup as claimed in claim 1, wherein the optical pickup uses a differential push-pull (DPP) method for tracking servo control.
14. The optical pickup as claimed in claim 2, wherein the numerical aperture of the objective lens is approximately 0.85.
15. The method of claim 6, comprising detecting a radial tilt signal from the multilayer recording medium, preventing crosstalk created by the beam reflected from the defocus layer.
16. An optical pickup for recording andor reproducing data with respect to a multilayer recording medium having a plurality of recording layers, the optical pickup comprising:
a light source emitting a beam having a predetermined wavelength;
a diffraction unit separating the beam emitted from the light source into a main beam and at least one sub-beam; and
a photodetector having a main photodetector, detecting the main beam reflected from the multilayer recording medium, and at least one sub-photodetector detecting the at least one sub-beam,
wherein the main photodetector and the at least one sub-photodetector are separated a predetermined distance from one another preventing a defocus spot, formed by the beam reflected by a defocus recording layer adjacent to a recording layer that is subject to recording andor reproduction, from being detected by the at least one sub-photodetector, and
wherein an outer border of the defocus spot is tangential to an outer area of the sub photodetector that is not contacted by the sub-beam, and
wherein the predetermined distance between the main photodetector and the at least on sub-photodetector satisfies the following inequality:
Ds\u2267A2\u2212QR
wherein \u201cR\u201d is a radius of the beam spot formed by the beam reflected from the defocus recording layer, \u201cA\u201d is a width of the sub-photodetector, and \u201cQ\u201d is a coefficient indicating an allowable range of a DC offset of a sub-push-pull signal, and
wherein the coefficient Q is between 0.85-0.90 when the allowable range of the DC offset is not more than 5%.
17. The optical pickup as claimed in claim 16, wherein the radius R of the beam spot satisfies the following equation:
R
=
2
\u2a2f
d
sp
n
sp
\u2a2f
M
\u2a2f
NA
,
wherein, \u201cdsp\u201d is a thickness of a spacer layer between the defocus recording layer and a recording layer that is subject to recording andor reproduction, \u201cnsp\u201d is z refractive index of the spacer layer, \u201cM\u201d is z magnifying power of the optical pickup, and \u201cNA\u201d is z numerical aperture of an objective lens used in the optical pickup.
18. The optical pickup as claimed in claim 16, wherein the DC offset of the sub-push-pull signal decreases as the predetermined distance between the main photodetector and the at least one sub-photodetector increases.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method for constructing a database of atomic fingerprint descriptors, the method comprising the steps of:
(i) calculating the atomic fingerprint descriptor of a substrate, which is represented by the following equation 1;
(ii) predicting activation energy for an atomic position using an atomic descriptor;
(iii) predicting cytochrome P450-mediated metabolism using the predicted activation energy; and
(iv) comparing the predicted metabolism with experimental metabolism and storing whether the metabolism occurs:
Xabc\u2003\u2003Equation 1
wherein X is the chemical symbol of an atom; a is a bond indicator that indicates the number of atoms bonded; b is a ring indicator that indicates whether the atom is part of a ring; and c is an aromatic indicator that indicates whether the atom is an aromatic atom.
2. The method of claim 1, wherein the metabolism in step (iii) is aliphatic hydroxylation or aromatic hydroxylation.
3. The method of claim 1, wherein the metabolism in step (iii) is N-dealkylation, C-hydroxylation, N-oxidation or O-dealkylation.
4. The method of claim 1, wherein the cytochrome P450 enzyme is any one selected from the group consisting of CYP2E1, CYP3A4, CYP2B6, CYP2C8, CYP2C9, CYP1A1, CYP1A2, CYP2C19, CYP2D6, CYP1B1, and CYP2A6.
5. A method for predicting activation energy using an atomic fingerprint descriptor and an atomic descriptor, the method comprising the steps of:
(i) calculating the atomic fingerprint descriptor of a substrate, which is represented by the following equation 1;
IS (ii) comparing the calculated atomic fingerprint descriptor with the data, constructed by the method of any one of claims 1 to 4, to select an atomic position where cytochrome P450-mediated metabolism can occur; and
(iii) predicting activation energy for the selected atomic position using an atomic descriptor:
Xabc\u2003\u2003Equation 1
wherein X is the chemical symbol of an atom; a is a bond indicator that indicates the number of atoms bonded; b is a ring indicator that indicates whether the atom is part of a ring; and c is an aromatic indicator that indicates whether the atom is an aromatic atom.
6. The method of claim 5, wherein the metabolism in step (ii) is aliphatic hydroxylation or aromatic hydroxylation.
7. The method of claim 5, wherein the metabolism in step (ii) is N-dealkylation, C-hydroxylation, N-oxidation or O-dealkylation.
8. The method of claim 5, wherein the cytochrome P450 enzyme is any one selected from the group consisting of CYP2E1, CYP3A4, CYP2B6, CYP2C8, CYP2C9, CYP1A1, CYP1A2, CYP2C19, CYP2D6, CYP1B1, and CYP2A6.
9. The method of claim 5, wherein step (iii) comprises predicting the activation energy for cytochrome P450-mediated hydrogen abstraction from a substrate of the following formula 1 using the atomic descriptors \u03b4het, max(\u03b4heavy), \u03bcC\u2014H and
\u2211
i
R
.
C
.
\ue89e
\u03b1
i
:
wherein the circle together with Fe\u2014O indicates an oxyferryl intermediate; \u03b4het indicates the net atomic charge of a heteroatom in the alpha-position relative to the reaction center; max(\u03b4heavy) indicates the highest atomic charge in X1, X2 and X3 which are neither hydrogen nor helium; \u03bcC\u2014H indicates the bond dipole of the carbon-hydrogen bond; and
\u2211
i
R
.
C
.
\ue89e
\u03b1
i
indicates the sum of the atomic polarizabilities of H, C, X1, X2 and X3.
10. The method of claim 9, wherein the activation energy is predicted according to the following equation:
EaHabs\u2014(B)=25.94+1.88*\u03b4het+1.03*max(\u03b4heavy)
wherein EaHabs\u2014(B) indicates activation energy required for abstraction of hydrogen attached to a carbon atom having a heteroatom in the alpha-position relative to the reaction center.
11. The method of claim 9, wherein the activation energy is predicted according to the following equation:
E
a
Habs_
\ue89e
(
A
)
=
28.50
–
2.22
*
\u03bc
C
–
H
+
1.12
*
\u2211
i
R
.
C
.
\ue89e
\u03b1
i
wherein EaHabs\u2014(A) indicates activation energy required for abstraction of hydrogen attached to a carbon atom having no heteroatom in the alpha-position relative to the reaction center.
12. The method of claim 5, wherein step (iii) comprises predicting the activation energy for tetrahedral intermediate formation in cytochrome P450-mediated aromatic hydroxylation for a substrate of the following formula using the atomic descriptors \u03b4H and mean(\u03b1alpha):
wherein the circle together with Fe\u2014O indicates an oxyferryl intermediate; \u03b4H indicates the net atomic charge of the hydrogen of the substrate; and mean(\u03b1alpha) indicates the mean value of the polarizabilities of adjacent carbon atoms.
13. The method of claim 12, wherein the activation energy is predicted according to the following equations:
Eaaro\u2014o,p=21.34\u22120.75*\u03b4H\u22121.24*(mean(\u03b1alpha)
wherein Eaaro\u2014o,p indicates the activation energy for tetrahedral intermediate formation in a benzene having one substituent in the orthopara-position.
14. The method of claim 12, wherein the activation energy is predicted according to the following equations:
Eaaro\u2014m=22.14\u22120.68*\u03b4H\u22120.83*mean(\u03b1alpha)
wherein Eaaro\u2014m indicates the activation energy for tetrahedral intermediate formation in a benzene having one substituent in the meta-position.
15. The method of claim 12, wherein the activation energy is predicted according to the following equations:
Eaaro\u20140,2,3=21.02\u22121.49*\u03b4H\u22120.92*mean(\u03b1alpha)
wherein Eaaro\u20140,2,3 indicates the activation energy for tetrahedral intermediate formation in a benzene having 0, 2 or 3 substituents.
16. A method for predicting a metabolite using the activated energy predicted by the method of claim 5.
17. The method of claim 16, wherein an atomic position having the lowest activation energy is predicted as a position where metabolism occurs.
18. A method of predicting a drug-drug interaction through the activation energy predicted by the method of claim 5.
19. A method of predicting the activation energy for cytochrome P450-mediated hydrogen abstraction from a substrate of the following formula using the atomic descriptors \u03b4het, max (\u03b4heavy), \u03bcC\u2014H and
\u2211
i
R
.
C
.
\ue89e
\u03b1
i
:
wherein the circle together with Fe\u2014O indicates an oxyferryl intermediate; \u03b4het indicates the net atomic charge of a heteroatom in the alpha-position relative to the reaction center; max(\u03b4heavy) indicates the highest atomic charge in X1, X2 and X3 which are neither hydrogen nor helium; \u03bcC\u2014H indicates the bond dipole of the carbon-hydrogen bond; and
\u2211
i
R
.
C
.
\ue89e
\u03b1
i
indicates the sum of the atomic polarizabilities of the atoms H, C, X1, X2 and X3.
20. The method of claim 19, wherein the cytochrome P450 enzyme is any one selected from the group consisting of CYP2E1, CYP3A4, CYP2B6, CYP2C8, CYP2C9, CYP1A1, CYP1A2, CYP2C19, CYP2D6, CYP1B1, and CYP2A6.
21. The method of claim 19, wherein, if the C atom of any C\u2014H bond to a target molecule is aliphatic carbon, it is determined to be a position where hydrogen abstraction can Occur.
22. The method of claim 19, wherein, if there is a heteroatom in the alpha-position relative to the reaction center, the atomic descriptors \u03b4het and max (\u03b4heavy) are calculated.
23. The method of claim 19, wherein, if there is no heteroatom in the alpha-position relative to the reaction center, the atomic descriptors \u03bcC\u2014H and
\u2211
i
R
.
C
.
\ue89e
\u03b1
i
are calculated.
24. The method of claim 22, wherein the activation energy is predicted according to the following equation:
EaHabs\u2014(B)=25.94+1.88*\u03b4het+1.03*max(\u03b4heavy)
wherein EaHabs\u2014(B) indicates activation energy required for abstraction of hydrogen attached to a carbon atom having a heteroatom in the alpha-position relative to the reaction center.
25. The method of claim 23, wherein the activation energy is predicted according to the following equation:
E
a
Habs_
\ue89e
(
A
)
=
28.50
–
2.22
*
\u03bc
C
–
H
+
1.12
*
\u2211
i
R
.
C
.
\ue89e
\u03b1
i
wherein EaHabs\u2014(A) indicates activation energy required for abstraction of hydrogen attached to a carbon atom having no heteroatom in the alpha-position relative to the reaction center.
26. A method of predicting the relative rate of metabolism (k) according to the following Arrhenius equation using the activation energy predicted by the method of any one of claims 19 to 25:
k=Ae\u2212EaRT
wherein k is a reaction rate constant, A is a frequency factor, Ea is activation energy, R is a gas constant, and T is absolute temperature.
27. A method of predicting metabolic regioselectivity using the activation energy predicted by the method of any one of claims 19 to 25.
28. The method of claim 27, wherein the metabolic regioselectivity is predicted by predicting the relative rate of metabolism according to the Arrhenius equation using the predicted activation energy and substituting the predicted relative rate of metabolism into the following equation:
P
1
P
2
=
ES
1
ES
2
\ue89e
k
5
k
6
wherein P indicates the relative probability of formation of any metabolite of all possible metabolites of a substrate, E is an enzyme, S is a substrate, ES is an enzyme-substrate complex, ES is the concentration of the enzyme-substrate complex, and k is reaction rate constant.
29. A method of predicting the inhibition of metabolism using the activation energy predicted by the method of any one of claims 19 to 25.
30. A method of predicting a drug-drug interaction using the activation energy predicted by the method of any one of claims 19 to 25.
31. A method of predicting the activation energy for tetrahedral intermediate formation in cytochrome P450-mediated aromatic hydroxylation for a substrate of the following formula using the atomic descriptors \u03b4H and mean (\u03b1alpha):
wherein the circle together with Fe\u2014O indicates an oxyferryl intermediate; \u03b4H indicates the net atomic charge of the hydrogen of the substrate; and mean(\u03b1alpha) indicates the mean values of polarizabilities of adjacent carbon atoms.
32. The method of claim 31, wherein the cytochrome P450 enzyme is any one selected from the group consisting of CYP2E1, CYP3A4, CYP2B6, CYP2C8, CYP2C9, CYP1A1, CYP1A2, CYP2C19, CYP2D6, CYP1B1, and CYP2A6.
33. The method of claim 31, wherein, if the C atom of any C\u2014H bond to a target molecule is aliphatic carbon, it is determined to be a position where hydrogen abstraction occurs.
34. The method of claim 31, wherein the atomic descriptors \u03b4H and mean(\u03b1alpha) are calculated.
35. The method of claim 34, wherein the activation energy is predicted according to the following equation:
Eaaro\u2014o,p=21.34\u22120.75*\u03b4H\u22121.24*mean(\u03b1alpha
wherein Eaaro\u2014o,p indicates the activation energy for tetrahedral intermediate formation in a benzene having one substituent in the orthopara-position.
36. The method of claim 34, wherein the activation energy is predicted according to the following equation:
Eaaro\u2014m=22.14\u22120.68*\u03b4H\u22120.83*mean(\u03b1alpha)
wherein Eaaro\u2014m indicates the activation energy for tetrahedral intermediate formation in a benzene having one substituent in the meta-position.
37. The method of claim 34, wherein the activation energy is predicted according to the following equation:
Eaaro\u20140,2,3=21.02\u22121.49*\u03b4H\u22120.92*mean(\u03b1alpha)
wherein Eaaro\u20140,2,3 indicates the activation energy for tetrahedral intermediate formation in a benzene having 0, 2 or 3 substituents.
38. A method of predicting the relative rate of metabolism (k) according to the following Arrhenius equation using the activation energy predicted by the method of any one of claims 31 to 37:
k=Ae\u2212EaRT
wherein k is a reaction rate constant, A is a frequency factor, Ea is activation energy, R is a gas constant, and T is absolute temperature.
39. A method of inhibiting metabolic regioselectivity using the activation energy predicted by the method of any one of claims 31 to 37.
40. The method of claim 39, wherein the metabolic regioselectivity is predicted by predicting the relative rate of metabolism according to the Arrhenius equation using the predicted activation energy and substituting the predicted relative rate of metabolism into the following equation:
P
1
P
2
=
ES
1
ES
2
\ue89e
k
5
k
6
wherein P indicates the relative probability of formation of any metabolite of all possible metabolites of a substrate, E is an enzyme, S is a substrate, ES is an enzyme-substrate complex, ES is the concentration of the enzyme-substrate complex, and k is a reaction rate constant.
41. A method of predicting metabolic inhibition using the activation energy predicted by the method of any one of claims 31 to 37.
42. A method of predicting a drug-drug interaction using the activation energy predicted by the method of any one of claims 31 to 37.