Abstract
Objective: The objective of the study was to elucidate the structural activity of a natural DNA sequence modified by a hydrophobic base-pair which didn’t form Watson-Crick (W-C) hydrogen-bond. The modified unnatural base-pair (DNAM-D5SICS) was introduced in DNA sequences of 14-mer for molecular dynamics study in water solution.Methods: A 200 ns molecular-dynamics-simulation in orthogonal-box-water-solvent, using Particle-mesh-Ewald-method (PME) within periodic-boundary-condition (PBC) was performed by using AMBER-14 code. The force-field-ff12SB-force-field was used during the simulation while the force-field-parameters of modified base-pair, compatible to ff12SB-force-field, were calculated by Gaussian-09-code using ab-inito/Hartree-Fock-methodology. The code CPPTRAJ, (a module of AMBER-14) CURVE and Chimera were used in the analysis of the data.Results: Root mean square deviation (RMSD) of heavy atoms of the trajectory revealed that the structure of the equilibrated duplex was stable, sequence-dependent and had mixed DNA-conformation. A little distortion near to the neighbor of the modified base-pair in the duplex strand was observed. However, we got a stabilized structure of such type of duplex if we placed modified base-pair after the third place in the strand.Conclusion: The study concluded that the distortion produced by modified-base-pair in the overall structure of duplex was local while the confirmation of such type of duplex was mixed and maintained the Watson-Crick (W-C) integrity of DNA. The study would help in the use of hydrophobic base-pair materials in biotechnological applications and the understanding of their structure-function relationship.
Highlights
In recent years the use of modified hydrophobic base-pair has been developed as the most fascinating technique in the genetic engineering [1, 2]
The structural conformational details of the study have reached on following conclusions [8, 10] (i) The mechanism of the insertion of DNAMTP opposite d5SICS was less efficient than the insertion of D5SICSTP opposite DNAM in starting replication.(ii) The nucleobases paired in an intercalated manner, similar to their pairing in free duplex DNA and the mode of pairing depends on the length of the single-stranded template, and (iii) more importantly, the mode of intercalation appeared to depend mostly on sequencespecific interactions of the flanking nucleotides, with the specific packing interactions between the intercalating nucleobases of secondary importance
As an attempts to characterize the conformation of hydrophobic, unnatural base-pair, the conformational parameters of the complexes leading to the insertion of DNAM opposite to D5sics in DNA-duplex we modelled 14-mer DNA strands of sequences d(GTCDNAM GCGCCGTGGC). d(GCCACGGCGCD5SICSGAC) in intrinsic solution and is reported here
Summary
In recent years the use of modified hydrophobic base-pair has been developed as the most fascinating technique in the genetic engineering [1, 2]. The structural conformational details of the study have reached on following conclusions [8, 10] (i) The mechanism of the insertion of DNAMTP opposite d5SICS was less efficient than the insertion of D5SICSTP opposite DNAM in starting replication.(ii) The nucleobases paired in an intercalated manner, similar to their pairing in free duplex DNA and the mode of pairing depends on the length of the single-stranded template, and (iii) more importantly, the mode of intercalation appeared to depend mostly on sequencespecific interactions of the flanking nucleotides, with the specific packing interactions between the intercalating nucleobases of secondary importance. Are limited to an insertion of DNAM and 5SICS in XACCAGGGCGCY (12-mer primer, and corresponding templet and 'X' represents purines and 'Y' represents DNAM or D5SICS) in different crystal and NMR
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