Molecular Dynamics Study of DNA Duplex Containing Carbazole-Derived Universal Base

2012 ◽  
Vol 506 ◽  
pp. 258-261
Author(s):  
W. Soodsawang ◽  
T. Benchawan ◽  
U. Wichai ◽  
Y. Tantirungrotechai
Keyword(s):  
Molecular Dynamics ◽  
Md Simulations ◽  
Reference Sequence ◽  
Dna Duplexes ◽  
Structure And Dynamics ◽  
Duplex Stability ◽  
Stability Order ◽  
The Stability ◽  
Duplex Formation ◽  
Universal Bases

Universal base is a man-made residue that can be incorporated into the DNA double strands without any discrimination against natural bases (A, C, G, T). The MD simulations with AMBER99 force field were employed to investigate the structure and dynamics of the modified 15-mer DNA duplexes containing carbazole-derived universal bases: carbazole (CBZ), 3,6-dicyanocarbazole (DCC), 3,6-dinitrocarbazole (DNC), and 3-nitro-6-cyanocarbazole (NCC), where X = CBZ, DCC, DNC, or NCC, respectively. The RMSD and B-factor of the modified DNAs backbones around the universal base unit fluctuate more than the reference sequence in the same position. The thermodynamic parameter for duplex stability was estimated by using MM-PBSA method. The averaged duplex formation free energy (ΔG) of all modified DNAs exhibited that the stability order was approximately DNC>NCC>CBZ>DCC, which differed from the reference sequence exceptional DNC unit. The averaged ΔG value of the DNC unit is very close to that of the reference sequence. This calculation indicated that the DNC unit can be considered as a good candidate for using as a universal base.

scholarly journals Nearest-neighbor parameters for predicting DNA duplex stability in diverse molecular crowding conditions

2020 ◽  
Vol 117 (25) ◽  
pp. 14194-14201 ◽  
Author(s):  
Saptarshi Ghosh ◽  
Shuntaro Takahashi ◽  
Tatsuya Ohyama ◽  
Tamaki Endoh ◽  
Hisae Tateishi-Karimata ◽  
...  
Keyword(s):  
Nearest Neighbor ◽  
Average Molecular Weight ◽  
Molecular Crowding ◽  
Dna Duplexes ◽  
Dna Duplex ◽  
Intracellular Environment ◽  
Duplex Stability ◽  
Key Factor ◽  
The Stability ◽  
Duplex Formation

The intracellular environment is crowded and heterogeneous. Although the thermodynamic stability of nucleic acid duplexes is predictable in dilute solutions, methods of predicting such stability under specific intracellular conditions are not yet available. We recently showed that the nearest-neighbor model for self-complementary DNA is valid under molecular crowding condition of 40% polyethylene glycol with an average molecular weight of 200 (PEG 200) in 100 mM NaCl. Here, we determined nearest-neighbor parameters for DNA duplex formation under the same crowding condition to predict the thermodynamics of DNA duplexes in the intracellular environment. Preferential hydration of the nucleotides was found to be the key factor for nearest-neighbor parameters in the crowding condition. The determined parameters were shown to predict the thermodynamic parameters (∆H°, ∆S°, and ∆G°37) and melting temperatures (Tm) of the DNA duplexes in the crowding condition with significant accuracy. Moreover, we proposed a general method for predicting the stability of short DNA duplexes in different cosolutes based on the relationship between duplex stability and the water activity of the cosolute solution. The method described herein would be valuable for investigating biological processes that occur under specific intracellular crowded conditions and for the application of DNA-based biotechnologies in crowded environments.

scholarly journals Structural Properties of G,T-Parallel Duplexes

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Anna Aviñó ◽  
Elena Cubero ◽  
Raimundo Gargallo ◽  
Carlos González ◽  
Modesto Orozco ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Structural Properties ◽  
Theoretical Calculations ◽  
Md Simulations ◽  
Theoretical Studies ◽  
Duplex Structure ◽  
Strong Stabilization ◽  
The Stability ◽  
The Impact

The structure of G,T-parallel-stranded duplexes of DNA carrying similar amounts of adenine and guanine residues is studied by means of molecular dynamics (MD) simulations and UV- and CD spectroscopies. In addition the impact of the substitution of adenine by 8-aminoadenine and guanine by 8-aminoguanine is analyzed. The presence of 8-aminoadenine and 8-aminoguanine stabilizes the parallel duplex structure. Binding of these oligonucleotides to their target polypyrimidine sequences to form the corresponding G,T-parallel triplex was not observed. Instead, when unmodified parallel-stranded duplexes were mixed with their polypyrimidine target, an interstrand Watson-Crick duplex was formed. As predicted by theoretical calculations parallel-stranded duplexes carrying 8-aminopurines did not bind to their target. The preference for the parallel-duplex over the Watson-Crick antiparallel duplex is attributed to the strong stabilization of the parallel duplex produced by the 8-aminopurines. Theoretical studies show that the isomorphism of the triads is crucial for the stability of the parallel triplex.

scholarly journals Atomistic Analysis of ToxN and ToxI Complex Unbinding Mechanism

2018 ◽  
Vol 19 (11) ◽  
pp. 3524 ◽  
Author(s):  
Guodong Hu ◽  
Xiu Yu ◽  
Yunqiang Bian ◽  
Zanxia Cao ◽  
Shicai Xu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Noncoding Rna ◽  
Md Simulations ◽  
Normal Function ◽  
Toxin Complex ◽  
Potentials Of Mean Force ◽  
Protein Toxins ◽  
Function Relationship ◽  
The Stability ◽  
Smd Simulations

ToxIN is a triangular structure formed by three protein toxins (ToxNs) and three specific noncoding RNA antitoxins (ToxIs). To respond to stimuli, ToxI is preferentially degraded, releasing the ToxN. Thus, the dynamic character is essential in the normal function interactions between ToxN and ToxI. Here, equilibrated molecular dynamics (MD) simulations were performed to study the stability of ToxN and ToxI. The results indicate that ToxI adjusts the conformation of 3′ and 5′ termini to bind to ToxN. Steered molecular dynamics (SMD) simulations combined with the recently developed thermodynamic integration in 3nD (TI3nD) method were carried out to investigate ToxN unbinding from the ToxIN complex. The potentials of mean force (PMFs) and atomistic pictures suggest the unbinding mechanism as follows: (1) dissociation of the 5′ terminus from ToxN, (2) missing the interactions involved in the 3′ terminus of ToxI without three nucleotides (G31, A32, and A33), (3) starting to unfold for ToxI, (4) leaving the binding package of ToxN for three nucleotides of ToxI, (5) unfolding of ToxI. This work provides information on the structure-function relationship at the atomistic level, which is helpful for designing new potent antibacterial drugs in the future.

scholarly journals Sorption, Structure and Dynamics of CO2 and Ethane in Silicalite at High Pressure: A Combined Monte Carlo and Molecular Dynamics Simulation Study

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 99 ◽  
Author(s):  
Siddharth Gautam ◽  
Tingting Liu ◽  
David Cole
Keyword(s):  
Molecular Dynamics ◽  
Monte Carlo ◽  
Time Scales ◽  
Rotational Motion ◽  
High Pressures ◽  
Sorption Isotherms ◽  
Md Simulations ◽  
Dynamics Simulation ◽  
Structure And Dynamics ◽  
Low Pressures

Silicalite is an important nanoporous material that finds applications in several industries, including gas separation and catalysis. While the sorption, structure, and dynamics of several molecules confined in the pores of silicalite have been reported, most of these studies have been restricted to low pressures. Here we report a comparative study of sorption, structure, and dynamics of CO2 and ethane in silicalite at high pressures (up to 100 bar) using a combination of Monte Carlo (MC) and molecular dynamics (MD) simulations. The behavior of the two fluids is studied in terms of the simulated sorption isotherms, the positional and orientational distribution of sorbed molecules in silicalite, and their translational diffusion, vibrational spectra, and rotational motion. Both CO2 and ethane are found to exhibit orientational ordering in silicalite pores; however, at high pressures, while CO2 prefers to reside in the channel intersections, ethane molecules reside mostly in the sinusoidal channels. While CO2 exhibits a higher self-diffusion coefficient than ethane at low pressures, at high pressures, it becomes slower than ethane. Both CO2 and ethane exhibit rotational motion at two time scales. At both time scales, the rotational motion of ethane is faster. The differences observed here in the behavior of CO2 and ethane in silicalite pores can be seen as a consequence of an interplay of the kinetic diameter of the two molecules and the quadrupole moment of CO2.

scholarly journals Structure and Dynamics of Glycosphingolipids in Lipid Bilayers: Insights from Molecular Dynamics Simulations

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Ronak Y. Patel ◽  
Petety V. Balaji
Keyword(s):  
Molecular Dynamics ◽  
Lipid Bilayers ◽  
Membrane Structure ◽  
Lipid Membrane ◽  
Biological Membranes ◽  
Md Simulations ◽  
Atomic Level ◽  
Structure And Dynamics ◽  
Hydrogen Bonding Interactions ◽  
Dynamics Simulations

Glycolipids are important constituents of biological membranes, and understanding their structure and dynamics in lipid bilayers provides insights into their physiological and pathological roles. Experimental techniques have provided details into their behavior at model and biological membranes; however, computer simulations are needed to gain atomic level insights. This paper summarizes the insights obtained from MD simulations into the conformational and orientational dynamics of glycosphingolipids and their exposure, hydration, and hydrogen-bonding interactions in membrane environment. The organization of glycosphingolipids in raft-like membranes and their modulation of lipid membrane structure are also reviewed.

Force field development and simulations of senior dialkyl sulfoxides

2016 ◽  
Vol 18 (15) ◽  
pp. 10507-10515 ◽  
Author(s):  
Vitaly V. Chaban
Keyword(s):  
Molecular Dynamics ◽  
Force Field ◽  
Ab Initio ◽  
Md Simulations ◽  
Field Development ◽  
Force Field Development ◽  
Structure And Dynamics ◽  
Ethyl Methyl ◽  
Methyl Sulfoxide ◽  
Diethyl Sulfoxide

Thermodynamics, structure, and dynamics of diethyl sulfoxide (DESO) and ethyl methyl sulfoxide (EMSO) were investigated using ab initio calculations and non-polarizable potential based molecular dynamics (MD) simulations.

scholarly journals Stability of Two-quartet G-quadruplexes and Their Dimers in Atomistic Simulations

2019 ◽  
Author(s):  
Barira Islam ◽  
Petr Stadlbauer ◽  
Michaela Vorlíčková ◽  
Jean-Louis Mergny ◽  
Michal Otyepka ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Md Simulations ◽  
The Other ◽  
Atomistic Simulations ◽  
Structural Element ◽  
Dna And Rna ◽  
Open Issue ◽  
Water Models ◽  
Weakly Stable ◽  
The Stability

ABSTRACTG-quadruplexes (GQs) are four-stranded non-canonical DNA and RNA architectures that can be formed by guanine-rich sequences. The stability of GQs increases with the number of G-quartets and three G-quartets generally form stable GQs. However, the stability of two-quartet GQs is an open issue. To understand the intrinsic stability of two-quartet GQ stems, we have carried out a series of unbiased molecular dynamics (MD) simulations (∼505 µs in total) of two- and four-quartet DNA and RNA GQs, with attention paid mainly to parallel-stranded arrangements. We used AMBER DNA parmOL15 and RNA parmOL3 force fields and tested different ion and water models. DNA two-quartet parallel-stranded GQs unfolded in all the simulations while the equivalent RNA GQ was stable in most of the simulations. GQs composed of two stacked units of two-quartet GQs were stable for both DNA and RNA. The simulations suggest that a minimum of three quartets are needed to form an intrinsically stable all-anti parallel-stranded DNA GQ. Parallel two-quartet DNA GQ may exist if substantially stabilized by another molecule or structural element, including multimerisation. On the other hand, we predict that isolated RNA two-quartet parallel GQs may form, albeit being weakly stable. We also show that ionic parameters and water models should be chosen with caution because some parameter combinations can cause spurious instability of GQ stems. Some in-so-far unnoticed limitations of force-field description of multiple ions inside the GQs are discussed, which compromise capability of simulations to fully capture the effect of increase of the number of quartets on the GQ stability.

scholarly journals Sequence-to-structure dependence of isolated IgG Fc complex biantennary N-glycans: A molecular dynamics study

2018 ◽  
Author(s):  
Aoife M Harbison ◽  
Lorna P Brosnan ◽  
Keith Fenlon ◽  
Elisa Fadda
Keyword(s):  
Molecular Dynamics ◽  
Structural Integrity ◽  
Md Simulations ◽  
Structure And Dynamics ◽  
Differential Recognition ◽  
Dependent Cell ◽  
Function Relationship ◽  
Simulation Time ◽  
Core Fucosylation

AbstractFc glycosylation of human immunoglobulins G (IgGs) is essential for their structural integrity and activity. Interestingly, the specific nature of the Fc glycoforms is known to modulate the IgG effector function. Indeed, while core-fucosylation of IgG Fc-glycans greatly affects the antibody-dependent cell-mediated cytotoxicity (ADCC) function, with obvious repercussions in the design of therapeutic antibodies, sialylation can reverse the antibody inflammatory response, and galactosylation levels have been linked to aging, to the onset of inflammation, and to the predisposition to rheumatoid arthritis. Within the framework of a structure-to-function relationship, we have studied the role of the N-glycan sequence on its intrinsic conformational propensity. Here we report the results of a systematic study, based on extensive molecular dynamics (MD) simulations in excess of 62 µs of cumulative simulation time, on the effect of sequence on the structure and dynamics of increasingly larger, complex biantennary N-glycoforms, i.e. from chitobiose to the larger N-glycan species commonly found in the Fc region of human IgGs. Our results show that while core fucosylation and sialylation do not affect the intrinsic dynamics of the isolated (unbound) N-glycans, galactosylation of the α(1-6) arm shifts dramatically its conformational equilibrium from an outstretched to a folded conformation. These findings are in agreement with and can help rationalize recent experimental evidence showing a differential recognition of positional isomers in glycan array data and also the preference of sialyltransferase for the more reachable, outstretched α(1-3) arm in both isolated and Fc-bound N-glycans.

scholarly journals A molecular dynamics study on the diffusion and imprint ability of spectinomycin under different sizes of aniline oligomers

2022 ◽  
Author(s):  
Chanadan Douykhumklaw ◽  
Thana Sutthibutpong
Keyword(s):  
Molecular Dynamics ◽  
Diffusion Coefficient ◽  
Mean Square Displacement ◽  
Md Simulations ◽  
Template Molecule ◽  
Aniline Oligomers ◽  
The Mean ◽  
The Stability ◽  
Further Development ◽  
Aniline Oligomer

Abstract Molecularly imprinted polymers (MIP) are the polymers created by molecular imprinting techniques that leave cavities for the specific interactions with a template molecule, and have been applied in molecular selectivity tasks. In this study, the molecular dynamics (MD) simulation technique was used to demonstrate that aniline oligomer could be developed as a potential MIP for detection and separation of the spectinomycin drug molecule for gonorrhoea treatment. MD simulations were performed for the systems of a spectinomycin within aniline oligomers of different sizes. The mean square displacement (MSD) and the diffusivity calculated from MD simulations showed that the diffusion coefficient was significantly dropped when the length of aniline oligomer was greater than two. The diffusion coefficient of spectinomycin became the lowest within aniline trimers, corresponded to the highest atomic distribution of MIP around the template. Then, the specific cavity in MIP systems with and without spectinomycin were calculated to assess the stability of the cavity created by the template. The volume of a cavity created within the trimer system was closest to the spectinomycin volume, and therefore became the optimal oligomer size for further development of MIP.

scholarly journals Forever Young: Structural Stability of Telomeric Guanine-Quadruplexes in Presence of Oxidative DNA Lesions

2020 ◽  
Author(s):  
Tom Miclot ◽  
Camille Corbier ◽  
Alessio Terenzi ◽  
Cécilia Hognon ◽  
Stéphanie Grandemange ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Dynamics ◽  
Structural Stability ◽  
Md Simulations ◽  
Dna Lesions ◽  
Computational Investigation ◽  
Telomeric Dna ◽  
G Quadruplex ◽  
The Stability

AbstractHuman telomeric DNA (h-Telo), in G-quadruplex (G4) conformation, is characterized by a remarkable structural stability that confers it the capacity to resist to oxidative stress producing one or even clustered 8-oxoguanine lesions. We present a combined experimental/computational investigation, by using circular dichroism in aqueous solutions, cellular immunofluorescence assays and molecular dynamics (MD) simulations, that identifies the crucial role of the stability of G4s to oxidative lesions, related also to their biological role as inhibitors of telomerase, an enzyme overexpressed in most cancers associated to oxidative stress.

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