73
4 Raman optical Activity of Biological Samples
procedure in which the force field and Raman/RoA tensor invariants are computed
in separate steps the following order is recommended: for small molecules augcc-pvdZ//cc-pvtZ (Raman/RoA tensor invariants//geometry and force fields),
for medium size molecules aug(sp)-cc-pvdZ//cc-pvtZ or rdPS//6-31g*, and for
large molecules the aug(sp)-cc-pvdZ//6-31g* or rdPS//6-31g* levels of theory
[69]. It was also shown that RoA simulation carried out using the hybrid functional B3LYP [74] is a reasonable compromise balancing the quality of results and
computer cost [75].
however, several challenges to the routine application of calculation of RoA
spectra still remain. Conformational flexibility, size of investigated molecule and
the strong effect of the solvent are the biggest problems to overcome. the total RoA
spectrum can be very dependent on the population of the different conformers. In
conformationally flexible molecules RoA signals arising from different conformations can cancel and so are not seen in the average RoA spectrum. thus, correct
determination of the relative energies for the relevant conformers is desirable for
rendering realistic RoA spectra. however this is difficult to achieve, especially for
molecules in solution when the influence of the solvent on the molecule is significant and needs to be taken into account. It is well known that a great advantage of
the RoA method is the possibility of exploring the conformational dynamics of
biomolecules in their native aqueous solution state. on the other hand, water is a
capricious solvent to model, mainly because of its ability to make hydrogen bonds.
In the current literature are presented several approaches to the modelling of solvent effects. generally, they can be divided into implicit solvent models, where the
solvent is defined as continuous medium and explicit solvent models, where the
calculations are performed for a cluster containing the studied molecule surrounded
by solvent molecules [60, 61, 76–80]. It has been recently shown that the use of
the latter models can lead to better results for hydrated hydrogen bond-forming
molecules [42, 76, 77].
Another challenging task is the calculation of RoA spectra for very large systems. In recent years full calculations for such big molecules have become possible
and some scientists have taken up this challenge. So far, the largest systems interpreted by quantum-chemical procedures are helical decaalanine [81], valinomycin
[82, 83], the β domain of metallothionein [84], a polypeptide of 20 alanine residues
(Ala) 20 in an α-helical conformation [85] and the hormone insulin [86]. until now,
insulin is the biggest molecule for which an RoA spectrum was computed by quantum chemical calculations and this simulation predicted correctly the experimental
spectroscopic response. the calculations on the insulin monomer and dimer were
possible by using a popular approximation, the so-called Cartesian–coordinate tensor transfer method [87]. In this method the original large target molecule is divided
into smaller molecular fragments for which the property tensors (force field, RoA
polarizabilities, etc.) are calculated and in the next step are transferred back to the
original molecule.
4 Raman optical Activity of Biological Samples
procedure in which the force field and Raman/RoA tensor invariants are computed
in separate steps the following order is recommended: for small molecules augcc-pvdZ//cc-pvtZ (Raman/RoA tensor invariants//geometry and force fields),
for medium size molecules aug(sp)-cc-pvdZ//cc-pvtZ or rdPS//6-31g*, and for
large molecules the aug(sp)-cc-pvdZ//6-31g* or rdPS//6-31g* levels of theory
[69]. It was also shown that RoA simulation carried out using the hybrid functional B3LYP [74] is a reasonable compromise balancing the quality of results and
computer cost [75].
however, several challenges to the routine application of calculation of RoA
spectra still remain. Conformational flexibility, size of investigated molecule and
the strong effect of the solvent are the biggest problems to overcome. the total RoA
spectrum can be very dependent on the population of the different conformers. In
conformationally flexible molecules RoA signals arising from different conformations can cancel and so are not seen in the average RoA spectrum. thus, correct
determination of the relative energies for the relevant conformers is desirable for
rendering realistic RoA spectra. however this is difficult to achieve, especially for
molecules in solution when the influence of the solvent on the molecule is significant and needs to be taken into account. It is well known that a great advantage of
the RoA method is the possibility of exploring the conformational dynamics of
biomolecules in their native aqueous solution state. on the other hand, water is a
capricious solvent to model, mainly because of its ability to make hydrogen bonds.
In the current literature are presented several approaches to the modelling of solvent effects. generally, they can be divided into implicit solvent models, where the
solvent is defined as continuous medium and explicit solvent models, where the
calculations are performed for a cluster containing the studied molecule surrounded
by solvent molecules [60, 61, 76–80]. It has been recently shown that the use of
the latter models can lead to better results for hydrated hydrogen bond-forming
molecules [42, 76, 77].
Another challenging task is the calculation of RoA spectra for very large systems. In recent years full calculations for such big molecules have become possible
and some scientists have taken up this challenge. So far, the largest systems interpreted by quantum-chemical procedures are helical decaalanine [81], valinomycin
[82, 83], the β domain of metallothionein [84], a polypeptide of 20 alanine residues
(Ala) 20 in an α-helical conformation [85] and the hormone insulin [86]. until now,
insulin is the biggest molecule for which an RoA spectrum was computed by quantum chemical calculations and this simulation predicted correctly the experimental
spectroscopic response. the calculations on the insulin monomer and dimer were
possible by using a popular approximation, the so-called Cartesian–coordinate tensor transfer method [87]. In this method the original large target molecule is divided
into smaller molecular fragments for which the property tensors (force field, RoA
polarizabilities, etc.) are calculated and in the next step are transferred back to the
original molecule.