190
4 Toward More Sophisticated Problems
The calculated reaction-energy profile based on a combined examination of
quantum mechanical and molecular mechanical (QM/MM) methodologies with the
DFT/UB3LYP/B1, B2, and B3 (see Sects. 3.2 and 3.6) for QM and the CHARMM22
force field for MM (see Sects. 3.4 and 3.6) implies that Mechanism II is the more
favorable, in which the initial O–O bond cleavage is followed by a proton transfer
with a simultaneous electron transfer to yield Compound 1 (Zheng et al. 2006). The
calculation results have predicted that the energy barrier of O–O bond cleavage as
the rate-determining step is about 13–14 kcal/mol in Mechanism II and that proton is
plausibly supplied via Asp 251 channel connected to the protein surface. On the other
hand, all the reaction paths in Mechanism I requires large activation energies. This
analysis is an example of clarification of enzyme reaction near its active site by the
calculation.
4.4.2 MD Simulation of Viruses
Along with the recent explosive acceleration of capability of computational
resources, the system size and the length for simulation time by the molecular
dynamics (MD) calculation has been much enhanced. Recent target system by the
MD analysis includes more than ten million atoms and to simulate the motion of the
total system in μs order. This is essential for analyses of large-scale systems such
as viruses in the biological field. The current computational situation has made it
possible to treat such huge biological systems compared with the past by the MD
calculations and two examples are to be given in what follows.
4.4.2.1 Satellite Tobacco Mosaic Virus (STMV)
The first all-atom molecular dynamics (MD) simulation of the satellite tobacco
mosaic virus (STMV) shown in Fig. 4.49 has been carried out (Freddolino et al.
2006). The STMV dealt with consists of a small icosahedral capsid with diameter
16 nm composed of 60 proteins (each MW = 14,500) and an RNA with 1058 base
pairs. The MD simulation is performed with the use of CHARMM22 force field for
proteins, CHARMM27 for nucleic acids, and TIP3P for water molecules. The total
number of atoms is about 1 million including water molecules as the solvent.
Simulation for the period of 13 ns has been performed to find that capsid is
structurally stabilized by presence of RNA in accordance with the hypothesis based
on the experimental evidence (Kuznetsov et al. 2005). In Fig. 4.50, the collapse
behavior of capsid in the absence of RNA is shown. Moreover, it has been found out
Mg
2+ ions added for compensation of negative charge of RNA were attaching to the
RNA during the simulation time.
4 Toward More Sophisticated Problems
The calculated reaction-energy profile based on a combined examination of
quantum mechanical and molecular mechanical (QM/MM) methodologies with the
DFT/UB3LYP/B1, B2, and B3 (see Sects. 3.2 and 3.6) for QM and the CHARMM22
force field for MM (see Sects. 3.4 and 3.6) implies that Mechanism II is the more
favorable, in which the initial O–O bond cleavage is followed by a proton transfer
with a simultaneous electron transfer to yield Compound 1 (Zheng et al. 2006). The
calculation results have predicted that the energy barrier of O–O bond cleavage as
the rate-determining step is about 13–14 kcal/mol in Mechanism II and that proton is
plausibly supplied via Asp 251 channel connected to the protein surface. On the other
hand, all the reaction paths in Mechanism I requires large activation energies. This
analysis is an example of clarification of enzyme reaction near its active site by the
calculation.
4.4.2 MD Simulation of Viruses
Along with the recent explosive acceleration of capability of computational
resources, the system size and the length for simulation time by the molecular
dynamics (MD) calculation has been much enhanced. Recent target system by the
MD analysis includes more than ten million atoms and to simulate the motion of the
total system in μs order. This is essential for analyses of large-scale systems such
as viruses in the biological field. The current computational situation has made it
possible to treat such huge biological systems compared with the past by the MD
calculations and two examples are to be given in what follows.
4.4.2.1 Satellite Tobacco Mosaic Virus (STMV)
The first all-atom molecular dynamics (MD) simulation of the satellite tobacco
mosaic virus (STMV) shown in Fig. 4.49 has been carried out (Freddolino et al.
2006). The STMV dealt with consists of a small icosahedral capsid with diameter
16 nm composed of 60 proteins (each MW = 14,500) and an RNA with 1058 base
pairs. The MD simulation is performed with the use of CHARMM22 force field for
proteins, CHARMM27 for nucleic acids, and TIP3P for water molecules. The total
number of atoms is about 1 million including water molecules as the solvent.
Simulation for the period of 13 ns has been performed to find that capsid is
structurally stabilized by presence of RNA in accordance with the hypothesis based
on the experimental evidence (Kuznetsov et al. 2005). In Fig. 4.50, the collapse
behavior of capsid in the absence of RNA is shown. Moreover, it has been found out
Mg
2+ ions added for compensation of negative charge of RNA were attaching to the
RNA during the simulation time.