Current Problems in Computer Simulation of Variability …
247
that conclusion [21]. For some base combinations computation predicts stacking
minima to be deeper than those for complexes with two H-bonds [21]. This observation suggests the necessity to refine the current FFs and to tune their predictions
to the experimental and the most reliable QM data.
5 Computational Problems with Elementary Units
of ‘Non-canonical’ Families of DNA
Extending the computational study of regularities of 3D structure of cdDMPs to DNA
fragments with two chains belonging to different conformation families encounter
additional challenges. Searching for various B-like conformations in NDB we found
four fragments of dGpdC:dGpdC sequence (NDB id BDL078, BDL084, 5EZF, and
5ET9) that have two complementary chains in the duplex being attributed to different
conformation families. Specifically, one chain of cdDMP belongs to BII family while
the complementary chain resembles BI conformation. In that structure, puckering of
3
-end sugar is intermediate between B and A families (conformation 32 or BI-to-A
according to Svozil classification [12]). These cdDMPs caught our attention because
their BII chains do not demonstrate base ring superposition typical for dDMPs in
BI, BII, AI and AII conformations, as well as for cdDMPs of the same sequence
when both their chains are in BI or AI conformation. DFT optimization of these
non-canonical cdDMPs using PW91 and PBE functionals leads to an inclination of
one of the base pairs followed by formation of H-bonds between the bases belonging
to different pairs that leads to significant deviation from the experimental structure.
Conducting the geometry optimization by using M05-2X and M06-2X functionals
reproduces the experimental conformation of the non-canonical cdDMP including
the base superposition patterns of two chains. However, the optimized structures
carry too short atom-atom contacts between the stacked bases.
Similar problems exist with the use of general-purpose DFT functionals, which
successfully reproduce the regularities in 3D structure formation of “classical” BI
and AI duplexes, but fail when applied to cdDMPs that have different B-like conformations in their two dDMPs. In those cases, SPB torsions remain in the regions of
initial family while the optimized cdDMPs configurations drastically differ from the
geometry of those fragments observed in the continuous DNA duplex. The use of
functionals specifically adjusted for stacking interactions as well as DFT-D functionals produces structures having shortened atom-atom contacts between the neighbor
bases in the chain, and in many cases leads to the increase in base superposition. In
this work, we deal with two examples of cdDMPs that have one chain being in BI
conformation and the complementary chain in 117 or 110 conformation. The conformations of 117 family correspond to the local energy minimum of the elementary
SPB, while the SPB of 110 conformation family does not correspond to the energy
minimum of the free SPB unit. The initial conformation of both cdDMPs with PurPyr sequence has greater superposition of base rings in the chain of BI conformation
247
that conclusion [21]. For some base combinations computation predicts stacking
minima to be deeper than those for complexes with two H-bonds [21]. This observation suggests the necessity to refine the current FFs and to tune their predictions
to the experimental and the most reliable QM data.
5 Computational Problems with Elementary Units
of ‘Non-canonical’ Families of DNA
Extending the computational study of regularities of 3D structure of cdDMPs to DNA
fragments with two chains belonging to different conformation families encounter
additional challenges. Searching for various B-like conformations in NDB we found
four fragments of dGpdC:dGpdC sequence (NDB id BDL078, BDL084, 5EZF, and
5ET9) that have two complementary chains in the duplex being attributed to different
conformation families. Specifically, one chain of cdDMP belongs to BII family while
the complementary chain resembles BI conformation. In that structure, puckering of
3
-end sugar is intermediate between B and A families (conformation 32 or BI-to-A
according to Svozil classification [12]). These cdDMPs caught our attention because
their BII chains do not demonstrate base ring superposition typical for dDMPs in
BI, BII, AI and AII conformations, as well as for cdDMPs of the same sequence
when both their chains are in BI or AI conformation. DFT optimization of these
non-canonical cdDMPs using PW91 and PBE functionals leads to an inclination of
one of the base pairs followed by formation of H-bonds between the bases belonging
to different pairs that leads to significant deviation from the experimental structure.
Conducting the geometry optimization by using M05-2X and M06-2X functionals
reproduces the experimental conformation of the non-canonical cdDMP including
the base superposition patterns of two chains. However, the optimized structures
carry too short atom-atom contacts between the stacked bases.
Similar problems exist with the use of general-purpose DFT functionals, which
successfully reproduce the regularities in 3D structure formation of “classical” BI
and AI duplexes, but fail when applied to cdDMPs that have different B-like conformations in their two dDMPs. In those cases, SPB torsions remain in the regions of
initial family while the optimized cdDMPs configurations drastically differ from the
geometry of those fragments observed in the continuous DNA duplex. The use of
functionals specifically adjusted for stacking interactions as well as DFT-D functionals produces structures having shortened atom-atom contacts between the neighbor
bases in the chain, and in many cases leads to the increase in base superposition. In
this work, we deal with two examples of cdDMPs that have one chain being in BI
conformation and the complementary chain in 117 or 110 conformation. The conformations of 117 family correspond to the local energy minimum of the elementary
SPB, while the SPB of 110 conformation family does not correspond to the energy
minimum of the free SPB unit. The initial conformation of both cdDMPs with PurPyr sequence has greater superposition of base rings in the chain of BI conformation