scholarly journals Base pair opening within B-DNA: free energy pathways for GC and AT pairs from umbrella sampling simulations

2003 ◽  
Vol 31 (5) ◽  
pp. 1434-1443 ◽  
Author(s):  
E. Giudice
Keyword(s):  
Free Energy ◽  
Base Pair ◽  
Umbrella Sampling ◽  
Energy Pathways ◽  
Base Pair Opening

Examining Electrostatic Influences on Base-Flipping: A Comparison of TIP3P and GB Solvent Models

2013 ◽  
Vol 13 (1) ◽  
pp. 223-237 ◽  
Author(s):  
Allyn R. Brice ◽  
Brian N. Dominy
Keyword(s):  
Free Energy ◽  
Base Pair ◽  
Umbrella Sampling ◽  
Water Molecules ◽  
Implicit Solvent ◽  
Interaction Energies ◽  
Base Flipping ◽  
Solvent Models ◽  
Explicit Water ◽  
Implicit Solvent Models

AbstractRecently, it was demonstrated that implicit solvent models were capable of generating stable B-form DNA structures. Specifically, generalized Born (GB) implicit solvent models have improved regarding the solvation of conformational sampling of DNA [1,2]. Here, we examine the performance of the GBSW and GBMV models in CHARMM for characterizing base flipping free energy profiles of undamaged and damaged DNA bases. Umbrella sampling of the base flipping process was performed for the bases cytosine, uracil and xanthine. The umbrella sampling simulations were carried-out with both explicit (TIP3P) and implicit (GB) solvent in order to establish the impact of the solvent model on base flipping. Overall, base flipping potential of mean force (PMF) profiles generated with GB solvent resulted in a greater free energy difference of flipping than profiles generated with TIP3P. One of the significant differences between implicit and explicit solvent models is the approximation of solute-solvent interactions in implicit solvent models. We calculated electrostatic interaction energies between explicit water molecules and the base targeted for flipping. These interaction energies were calculated over the base flipping reaction coordinate to illustrate the stabilizing effect of the explicit water molecules on the flipped-out state. It is known that nucleic base pair hydrogen bonds also influenced the free energy of flipping since these favorable interactions must be broken in order for a base to flip-out of the helix. The Watson-Crick base pair hydrogen bond fractions were calculated over the umbrella sampling simulation windows in order to determine the effect of base pair interactions on the base flipping free energy. It is shown that interaction energies between the flipping base and explicit water molecules are responsible for the lower base flipping free energy difference in the explicit solvent PMF profiles.

Determination of Base Flipping Free Energy Landscapes from Nonequilibrium Stratification

2019 ◽  
Author(s):  
Xiaohui Wang ◽  
Zhaoxi Sun
Keyword(s):  
Free Energy ◽  
Energy Landscape ◽  
Sampling Technique ◽  
Umbrella Sampling ◽  
Energy Simulation ◽  
Nonlinear Dependence ◽  
Free Energy Landscape ◽  
Convergence Criterion ◽  
Base Flipping ◽  
Convergence Behavior

<p>Correct calculation of the variation of free energy upon base flipping is crucial in understanding the dynamics of DNA systems. The free energy landscape along the flipping pathway gives the thermodynamic stability and the flexibility of base-paired states. Although numerous free energy simulations are performed in the base flipping cases, no theoretically rigorous nonequilibrium techniques are devised and employed to investigate the thermodynamics of base flipping. In the current work, we report a general nonequilibrium stratification scheme for efficient calculation of the free energy landscape of base flipping in DNA duplex. We carefully monitor the convergence behavior of the equilibrium sampling based free energy simulation and the nonequilibrium stratification and determine the empirical length of time blocks required for converged sampling. Comparison between the performances of equilibrium umbrella sampling and nonequilibrium stratification is given. The results show that nonequilibrium free energy simulation is able to give similar accuracy and efficiency compared with the equilibrium enhanced sampling technique in the base flipping cases. We further test a convergence criterion we previously proposed and it comes out that the convergence behavior determined by this criterion agrees with those given by the time-invariant behavior of PMF and the nonlinear dependence of standard deviation on the sample size. </p>

scholarly journals Base-Pair Opening Dynamics Study of Fluoride Riboswitch in the Bacillus cereus CrcB Gene

2021 ◽  
Vol 22 (6) ◽  
pp. 3234
Author(s):  
Juhyun Lee ◽  
Si-Eun Sung ◽  
Janghyun Lee ◽  
Jin Young Kang ◽  
Joon-Hwa Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Nmr Spectroscopy ◽  
Bacillus Cereus ◽  
Base Pair ◽  
Noncoding Rna ◽  
Hydrogen Exchange ◽  
Magnesium Ion ◽  
Fluoride Ion ◽  
Base Pair Opening

Riboswitches are segments of noncoding RNA that bind with metabolites, resulting in a change in gene expression. To understand the molecular mechanism of gene regulation in a fluoride riboswitch, a base-pair opening dynamics study was performed with and without ligands using the Bacillus cereus fluoride riboswitch. We demonstrate that the structural stability of the fluoride riboswitch is caused by two steps depending on ligands. Upon binding of a magnesium ion, significant changes in a conformation of the riboswitch occur, resulting in the greatest increase in their stability and changes in dynamics by a fluoride ion. Examining hydrogen exchange dynamics through NMR spectroscopy, we reveal that the stabilization of the U45·A37 base-pair due to the binding of the fluoride ion, by changing the dynamics while maintaining the structure, results in transcription regulation. Our results demonstrate that the opening dynamics and stabilities of a fluoride riboswitch in different ion states are essential for the genetic switching mechanism.

scholarly journals Base Pair Opening in a Deoxynucleotide Duplex Containing a cis-syn Thymine Cyclobutane Dimer Lesion

Biochemistry ◽  
2013 ◽  
Vol 52 (51) ◽  
pp. 9275-9285 ◽  
Author(s):  
Belinda B. Wenke ◽  
Leah N. Huiting ◽  
Elisa B. Frankel ◽  
Benjamin F. Lane ◽  
Megan E. Núñez
Keyword(s):  
Base Pair ◽  
Cyclobutane Dimer ◽  
Base Pair Opening

scholarly journals Rock climbing: A local-global algorithm to compute minimum energy and minimum free energy pathways

2017 ◽  
Vol 147 (15) ◽  
pp. 152718 ◽  
Author(s):  
Clark Templeton ◽  
Szu-Hua Chen ◽  
Arman Fathizadeh ◽  
Ron Elber
Keyword(s):  
Free Energy ◽  
Minimum Energy ◽  
Minimum Free Energy ◽  
Rock Climbing ◽  
Global Algorithm ◽  
Energy Pathways

scholarly journals Reduction in Dynamics of Base pair Opening upon Ligand Binding by the Cocaine-Binding Aptamer

2020 ◽  
Vol 119 (6) ◽  
pp. 1147-1156
Author(s):  
Zachary R. Churcher ◽  
Devid Garaev ◽  
Howard N. Hunter ◽  
Philip E. Johnson
Keyword(s):  
Ligand Binding ◽  
Base Pair ◽  
Base Pair Opening

Nucleation free-energy barriers with Hybrid Monte-Carlo/Umbrella Sampling

2014 ◽  
Vol 16 (45) ◽  
pp. 24913-24919 ◽  
Author(s):  
M. A. Gonzalez ◽  
E. Sanz ◽  
C. McBride ◽  
J. L. F. Abascal ◽  
C. Vega ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Free Energy ◽  
Umbrella Sampling ◽  
Energy Barriers ◽  
Hybrid Monte Carlo

scholarly journals Free energy landscape for the entire transport cycle of triose-phosphate/phosphate translocator

2017 ◽  
Author(s):  
Mizuki Takemoto ◽  
Yongchan Lee ◽  
Ryuichiro Ishitani ◽  
Osamu Nureki
Keyword(s):  
Free Energy ◽  
Conformational Changes ◽  
Conformational Transition ◽  
Substrate Binding ◽  
Energy Landscape ◽  
Umbrella Sampling ◽  
Free Energy Landscape ◽  
Coupling Mechanism ◽  
Triose Phosphate ◽  
Phosphate Translocator

AbstractSecondary active transporters translocate their substrates using the electrochemical potentials of other chemicals, undergoing large-scale conformational changes. Despite extensive structural studies, the atomic details of the transport mechanism still remain elusive. Here we performed a series of all-atom molecular dynamics simulations of the triose-phosphate/phosphate translocator (TPT), which exports organic phosphates in the chloroplast stroma in strict counter exchange with inorganic phosphate (Pi). Biased sampling methods, including string method and umbrella sampling, successfully reproduced the conformational changes between the inward– and outward-facing states, along with the substrate binding. The free energy landscape of this entire TPT transition pathway demonstrated the alternating access and substrate translocation mechanisms, which revealed Pi is relayed by positively charged residues along the transition pathway. Furthermore, the conserved Glu207 functions as a “molecular switch”, linking the local substrate binding and the global conformational transition. Our results provide atomic-detailed insights into the energy coupling mechanism of antiporter.

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