Interaction energy calculation system, method, and program
View Patent ↗A system computes the interaction energy between a plurality of fragments in a calculation object substance according to the fragment molecular orbital method. The energy of each fragment, the two-body interaction energy of each dimer including two fragments, and the three-body interaction energy of each trimer including three fragments are calculated. The two-body interaction energy of each dimer is corrected by adding, to the two-body interaction energy of the dimer, the contribution of the dimer in the three-body interaction energy of the trimer that includes the dimer.
1. An interaction energy calculation system for selecting a candidate compound based on the binding mechanism between a receptor composed of proteins and a candidate compound of a ligand to the receptor, the system comprising a control unit for calculating inter-fragment interaction energies between a plurality of monomers, which are fragments of molecules in a calculation object substance, by a fragment molecular orbital method, wherein the calculation object substance is a molecular complex including the receptor composed of proteins and the candidate compound of a ligand to the receptor,
wherein the control unit includes:
a central processing unit; and
a memory,
the control unit is configured to:
calculate the energy of each of the monomers,
calculate the total electronic energy E FMO2 based on the FMO2 method by calculating the two-body interaction energy of each of a plurality of dimers, each of the dimers including two of the monomers, where
E
FMO
2
=
∑
I
>
J
Δ
E
I
J
+
∑
I
E
I
=
∑
I
>
J
Δ
E
˜
I
J
+
∑
I
E
I
′
calculate the total electronic energy E FMO3 based on the FMO3 method by calculating the three-body interaction energy of each of a plurality of trimers, each of the trimers including three of the monomers, where
E
FMO
3
=
∑
I
>
J
>
K
Δ
E
~
I
J
K
+
∑
I
>
J
Δ
E
˜
I
J
+
∑
I
E
I
′
correct the two-body interaction energy for each dimer according to
Δ
E
˜
I
J
+
1
3
∑
K
Δ
E
˜
I
J
K
,
and
calculate the corrected two-body interaction energy as inter-fragment interaction energy in the dimer, wherein the control unit outputs the corrected inter-fragment interaction energy to an output device to provide the inter-fragment interaction energies between the plurality of monomers;
wherein the inter-fragment interaction energies illustrate the binding mechanism between the receptor and the candidate compound.
2. The interaction energy calculation system according to claim 1 , wherein
the control unit is further configured to:
calculate the total electronic energies E FMO4 based on the FMO4 method by calculating four-body interaction energy of each of a plurality of tetramers, each of the tetramers including four of the monomers, where
E
FMO
4
=
∑
I
>
J
>
K
>
L
Δ
E
˜
I
J
K
L
+
∑
I
>
J
>
K
Δ
E
˜
I
J
K
+
∑
I
>
J
Δ
E
˜
I
J
+
∑
I
E
I
′
and
for each dimer, correct the two-body interaction energy of the dimer according to
Δ
E
˜
I
J
+
1
3
∑
K
Δ
E
˜
I
J
K
+
1
6
∑
K
>
L
Δ
E
˜
I
J
K
L
,
, and
calculate the corrected two-body interaction energy as inter-fragment interaction energy in the dimer.
3. The interaction energy calculation system according to claim 1 , wherein
the control unit is further configured to:
divide the structure corresponding to the calculation object substance into a plurality of monomers,
divide the receptor structure corresponding to the receptor into a plurality of monomers each including at least a partial structure of an amino acid residue, and
divide the structure corresponding to the candidate compound of the ligand into a plurality of monomers.
4. The interaction energy calculation system according to claim 3 , wherein the control unit is further configured to divide the receptor structure into a monomer corresponding to a main chain of the amino acid residue and a monomer corresponding to a side chain of the amino acid residue.
5. The interaction energy calculation system according to claim 3 , wherein the control unit is further configured to divide the monomer corresponding to a side chain of the amino acid residue into one or more monomers.
6. The interaction energy calculation system according to claim 3 , wherein the control unit is further configured to divide the receptor structure into monomers at a site between the carbon atom in a carbonyl group of the amino acid residue and a carbon atom bonded to the carbon atom in the carbonyl group.
7. The interaction energy calculation system according to claim 3 , wherein the control unit is further configured to divide the receptor structure into monomers at a site between the nitrogen atom and the carbon atom in a peptide bond between the amino acid residues.
8. A method for selecting a candidate compound based on the binding mechanism between a receptor composed of proteins and a candidate compound of a ligand to the receptor by calculating inter-fragment interaction energies between a plurality of monomers, which are fragments of molecules in a calculation object substance, wherein the calculation object substance is a molecular complex including the receptor composed of proteins and the candidate compound of a ligand to the receptor by a control unit having a central processing unit and a memory with a fragment molecular orbital method, the method comprising:
calculating, by the control unit, the energy of each of the monomers,
calculating, by the control unit, the total electronic energy E FMO2 based on the FMO2 method by calculating the two-body interaction energy of each of a plurality of dimers, each of the dimers including two of the monomers, where
E
FMO
2
=
∑
I
>
J
Δ
E
I
J
+
∑
I
E
I
=
∑
I
>
J
Δ
E
˜
I
J
+
∑
I
E
I
′
calculating, by the control unit, the total electronic energy E FMO3 based on the FMO3 method by calculating the three-body interaction energy of each of a plurality of trimers, each of the trimers including three of the monomers, where
E
FMO
3
=
∑
I
>
J
>
K
Δ
E
~
I
J
K
+
∑
I
>
J
Δ
E
˜
I
J
+
∑
I
E
I
′
correcting, by the control unit, the two-body interaction energy for each dimer according to
Δ
E
˜
I
J
+
1
3
∑
K
Δ
E
˜
I
J
K
,
and
calculating, by the control unit, the corrected two-body interaction energy as inter-fragment interaction energy in the dimer;
wherein the inter-fragment interaction energies illustrate the binding mechanism between the receptor and the candidate compound.
9. A non-transitory computer-readable recording medium storing a program for selecting a candidate compound based on the binding mechanism between a receptor composed of proteins and a candidate compound of a ligand to the receptor by calculating inter-fragment interaction energies between a plurality of monomers, which are fragments of molecules by using a calculating system that includes a control unit for calculating inter-fragment interaction energies between a plurality of monomers in a calculation object substance, wherein the calculation object substance is a molecular complex including the receptor composed of proteins and the candidate compound of a ligand to the receptor by a fragment molecular orbital method, the control unit including a central processing unit and a memory,
wherein, when the program is executed, the computer-readable recording medium causes the control unit to:
calculate the energy of each of the monomers,
calculate the total electronic energy E FMO2 based on the FMO2 method by calculating the two-body interaction energy of each of a plurality of dimers, each of the dimers including two of the monomers, where
E
FMO
2
=
∑
I
>
J
Δ
E
I
J
+
∑
I
E
I
=
∑
I
>
J
Δ
E
˜
I
J
+
∑
I
E
I
′
calculate the total electronic energy E FMO3 based on the FMO3 method by calculating the three-body interaction energy of each of a plurality of trimers, each of the trimers including three of the monomers, where
E
FMO
3
=
∑
I
>
J
>
K
Δ
E
˜
I
J
K
+
∑
I
>
J
Δ
E
˜
I
J
+
∑
I
E
I
′
correct the two-body interaction energy for each dimer according to
Δ
E
˜
I
J
+
1
3
∑
K
Δ
E
˜
I
J
K
,
and
calculate the corrected two-body interaction energy as inter-fragment interaction energy in the dimer;
wherein the inter-fragment interaction energies illustrate the binding mechanism between the receptor and the candidate compound.