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1 Hybrid QM/MM Methods: Treating Electronic Phenomena …
1.6.1 Absorption of Human Serum Albumin (HSA)
HSA is a liver produced protein present in the blood where it exercises regulatory
and transport functions. Despite its huge mass, it only possesses one tryptophan
residue. Tryptophan is fluorescent and its optical properties are strongly dependent
on the environment. The latter can be used to probe their conformation. Indeed in
the protein (Fig. 1.2) the tryptophan is embedded in a pocket between different αhelices, in an environment strongly different from the one of the denatured protein
where it will be mainly surrounded by water molecules.
In Fig. 1.2 (right panel) one can also see the QM/MM absorption spectrum
computed at Time Dependent Density Functional (TD-DFT) level using B3LYP
exchange correlation functionals and a 6–311 + G(d, p) basis set [9]. The protein
environment where treated using amber99 force field. Note that the transitions have
been obtained as Franck-Condon vertical transitions from the ground state equilibrium geometry. The QM-MM frontier has been treated placing an SLBO between
the C α –C β bond of the tryptophan lateral chain.
The spectrum obtained with the three different embedding schemes [9] is provided and one can see that the computed spectrum presents two well defined absorption
maxima at about 250 and 275 nm, respectively. This represents a significant redshift compared to the absorption of water solvated tryptophan, accounting for the
environment effects. Notice also that the inclusion of polarization effects, treated
using the ERS technique, induces a non negligible shift over the ME and EE absorption maxima, confirming the fact that differently from the case of ground state
studies, in the case of electronic transitions all the three embedding effects should
be taken into account.
1.6.2 Absorption of Copper Proteins (From Red to Blue Protein)
Plastocyanin (Fig. 1.3) are metallo-protein present in superior plants were they assure electron-transfer during the photosynthetic process [57, 58]. The active site of
the protein is constituted by a copper ion complexed by four aminoacids residues:
one deprotonated cysteine, one methionine and two hystidines. Notice that the electron-transfer is assured by the copper atoms that can reversibly convert between the
+ II and + I form. QM–MM calculations have allowed us to show that the protein
environment regulates the necessary high rate of electron-transfer by constraining
the copper environment in a geometry that is somehow mid-way between the ones
of the + II and + I complex in gas phase [57] (i.e. copper coordinated by the lateral
chains of the previous cited aminoacids, only), moreover in the protein geometrical
differences between the oxidized and reduced form are extremely small, thus minimizing the reorganization energy of the redox process.
But oxidized plastocyanin are also known to exhibit a very peculiar absorption
spectrum, characterized by a very intense absorption at about 600 nm responsible
for the intense blue color, and quite different from the one of isolated copper com-
1 Hybrid QM/MM Methods: Treating Electronic Phenomena …
1.6.1 Absorption of Human Serum Albumin (HSA)
HSA is a liver produced protein present in the blood where it exercises regulatory
and transport functions. Despite its huge mass, it only possesses one tryptophan
residue. Tryptophan is fluorescent and its optical properties are strongly dependent
on the environment. The latter can be used to probe their conformation. Indeed in
the protein (Fig. 1.2) the tryptophan is embedded in a pocket between different αhelices, in an environment strongly different from the one of the denatured protein
where it will be mainly surrounded by water molecules.
In Fig. 1.2 (right panel) one can also see the QM/MM absorption spectrum
computed at Time Dependent Density Functional (TD-DFT) level using B3LYP
exchange correlation functionals and a 6–311 + G(d, p) basis set [9]. The protein
environment where treated using amber99 force field. Note that the transitions have
been obtained as Franck-Condon vertical transitions from the ground state equilibrium geometry. The QM-MM frontier has been treated placing an SLBO between
the C α –C β bond of the tryptophan lateral chain.
The spectrum obtained with the three different embedding schemes [9] is provided and one can see that the computed spectrum presents two well defined absorption
maxima at about 250 and 275 nm, respectively. This represents a significant redshift compared to the absorption of water solvated tryptophan, accounting for the
environment effects. Notice also that the inclusion of polarization effects, treated
using the ERS technique, induces a non negligible shift over the ME and EE absorption maxima, confirming the fact that differently from the case of ground state
studies, in the case of electronic transitions all the three embedding effects should
be taken into account.
1.6.2 Absorption of Copper Proteins (From Red to Blue Protein)
Plastocyanin (Fig. 1.3) are metallo-protein present in superior plants were they assure electron-transfer during the photosynthetic process [57, 58]. The active site of
the protein is constituted by a copper ion complexed by four aminoacids residues:
one deprotonated cysteine, one methionine and two hystidines. Notice that the electron-transfer is assured by the copper atoms that can reversibly convert between the
+ II and + I form. QM–MM calculations have allowed us to show that the protein
environment regulates the necessary high rate of electron-transfer by constraining
the copper environment in a geometry that is somehow mid-way between the ones
of the + II and + I complex in gas phase [57] (i.e. copper coordinated by the lateral
chains of the previous cited aminoacids, only), moreover in the protein geometrical
differences between the oxidized and reduced form are extremely small, thus minimizing the reorganization energy of the redox process.
But oxidized plastocyanin are also known to exhibit a very peculiar absorption
spectrum, characterized by a very intense absorption at about 600 nm responsible
for the intense blue color, and quite different from the one of isolated copper com-