Current Problems in Computer Simulation of Variability …
237
from those of Pyr–Pur and Pyr–Pyr structures corresponding to AI, AII, BI, and BII
conformation families of WCD. The base rings substantially overlap in the first pair
of sequences, whereas only a minor, if any, overlap exists in the second pair. These
regularities also occur in complementary dDMPs (cdDMPs), which are minimal
fragments of duplex, but only when both chains belong to one of the above mentioned
DNA conformation families [7, 8]. Other polynucleotide duplexes, such as lefthanded Z-forms, Hoogsteen and parallel-stranded duplexes, duplexes with mispairs
[4–8] do not demonstrate this regularity, which is important for biological function
of DNA.
Besides the duplexes mentioned above, the Nucleic acid Database, NDB [9, 10],
contains DNA fragments in the variety of other conformations, such as triplexes,
quadruplexes, Holliday junctions, etc. It appears that some fragments of DNA contain
cdDMPs with Watson-Crick nucleoside pairs having one or both chains of SPB
pertaining to conformation families different from A- and B- ones. Svozil et al. have
conducted a systematic classification and analysis of various conformation families
of minimal fragments of DNA single chain [11, 12].
This work is a continuation of our ongoing study of simple fragments of DNA
[2–8]. We discuss the variability of three-dimensional structure of DNA duplex with
Watson-Crick nucleoside pairs, the sources of this variability, and the problems of
application of various QM and MM methods to the understanding and predicting conformational characteristics of such DNA fragments constructed of various nucleotide
sequences.
2 Model Systems and Computational Methods
The main systems, which are considered in this work, are the minimal fragments
of DNA duplex (cdDMP), and those of the single chain (dDMP) neutralized by
sodium ions. Figure 2 presents the molecular structure and torsion angle designations of a sample minimal fragment of WCD, which is a complex of complementary
dinucleoside monophosphates dApdG and dTpdC. Na
+ ions are omitted in this and
next figures for clarity. For each fragment, an initial configuration was constructed
using atomic coordinates of the corresponding fragments of a structure obtained
from NDB [8, 9]. Hydrogen atoms and sodium ions were added in the position most
likely for a given atomic group. For evaluation of subunit contributions to the formation of three-dimensional structure of cdDMPs (and that of longer DNA fragments)
computations were performed on the minimal fragments of SPB having the bases in
dDMPs substituted by hydrogen atoms. Comparison of optimized and initial cdDMP
conformations conducted on select structures provide an estimate of contribution of
base-base interactions. Computations of selected pairwise interactions of separate
bases (1-methylpyrimidines and 9-methylpurines) locate the local energy minima
that provide reference points for the comparison.
We use MM and QM methods to compute energy and the local minima. The MM
method has traditionally been applied to molecular systems of substantially more
237
from those of Pyr–Pur and Pyr–Pyr structures corresponding to AI, AII, BI, and BII
conformation families of WCD. The base rings substantially overlap in the first pair
of sequences, whereas only a minor, if any, overlap exists in the second pair. These
regularities also occur in complementary dDMPs (cdDMPs), which are minimal
fragments of duplex, but only when both chains belong to one of the above mentioned
DNA conformation families [7, 8]. Other polynucleotide duplexes, such as lefthanded Z-forms, Hoogsteen and parallel-stranded duplexes, duplexes with mispairs
[4–8] do not demonstrate this regularity, which is important for biological function
of DNA.
Besides the duplexes mentioned above, the Nucleic acid Database, NDB [9, 10],
contains DNA fragments in the variety of other conformations, such as triplexes,
quadruplexes, Holliday junctions, etc. It appears that some fragments of DNA contain
cdDMPs with Watson-Crick nucleoside pairs having one or both chains of SPB
pertaining to conformation families different from A- and B- ones. Svozil et al. have
conducted a systematic classification and analysis of various conformation families
of minimal fragments of DNA single chain [11, 12].
This work is a continuation of our ongoing study of simple fragments of DNA
[2–8]. We discuss the variability of three-dimensional structure of DNA duplex with
Watson-Crick nucleoside pairs, the sources of this variability, and the problems of
application of various QM and MM methods to the understanding and predicting conformational characteristics of such DNA fragments constructed of various nucleotide
sequences.
2 Model Systems and Computational Methods
The main systems, which are considered in this work, are the minimal fragments
of DNA duplex (cdDMP), and those of the single chain (dDMP) neutralized by
sodium ions. Figure 2 presents the molecular structure and torsion angle designations of a sample minimal fragment of WCD, which is a complex of complementary
dinucleoside monophosphates dApdG and dTpdC. Na
+ ions are omitted in this and
next figures for clarity. For each fragment, an initial configuration was constructed
using atomic coordinates of the corresponding fragments of a structure obtained
from NDB [8, 9]. Hydrogen atoms and sodium ions were added in the position most
likely for a given atomic group. For evaluation of subunit contributions to the formation of three-dimensional structure of cdDMPs (and that of longer DNA fragments)
computations were performed on the minimal fragments of SPB having the bases in
dDMPs substituted by hydrogen atoms. Comparison of optimized and initial cdDMP
conformations conducted on select structures provide an estimate of contribution of
base-base interactions. Computations of selected pairwise interactions of separate
bases (1-methylpyrimidines and 9-methylpurines) locate the local energy minima
that provide reference points for the comparison.
We use MM and QM methods to compute energy and the local minima. The MM
method has traditionally been applied to molecular systems of substantially more