Reaction Coordinate and Thermodynamics of Base Flipping in RNA

<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>

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Faculty Opinions recommendation of DNA nicking by HinP1I endonuclease: bending, base flipping and minor groove expansion.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1031131.363548 ◽

2006 ◽

Author(s):

Alfred Pingoud

Keyword(s):

Minor Groove ◽

Base Flipping ◽

Dna Nicking

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Bimolecular Reactions, Transition-State Theory

10.1093/oso/9780198805014.003.0006 ◽

2018 ◽

Author(s):

Niels Engholm Henriksen ◽

Flemming Yssing Hansen

Keyword(s):

Transition State ◽

Saddle Point ◽

Transition State Theory ◽

Classical Mechanics ◽

Small Degree ◽

State Theory ◽

Reaction Coordinate ◽

Partition Functions ◽

Bimolecular Reactions ◽

Activated Complex

This chapter discusses an approximate approach—transition-state theory—to the calculation of rate constants for bimolecular reactions. A reaction coordinate is identified from a normal-mode coordinate analysis of the activated complex, that is, the supermolecule on the saddle-point of the potential energy surface. Motion along this coordinate is treated by classical mechanics and recrossings of the saddle point from the product to the reactant side are neglected, leading to the result of conventional transition-state theory expressed in terms of relevant partition functions. Various alternative derivations are presented. Corrections that incorporate quantum mechanical tunnelling along the reaction coordinate are described. Tunnelling through an Eckart barrier is discussed and the approximate Wigner tunnelling correction factor is derived in the limit of a small degree of tunnelling. It concludes with applications of transition-state theory to, for example, the F + H2 reaction, and comparisons with results based on quasi-classical mechanics as well as exact quantum mechanics.

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Joint Reaction Coordinate for Computing the Free-Energy Landscape of Pore Nucleation and Pore Expansion in Lipid Membranes

Journal of Chemical Theory and Computation ◽

10.1021/acs.jctc.0c01134 ◽

2021 ◽

Vol 17 (2) ◽

pp. 1229-1239

Author(s):

Jochen S. Hub

Keyword(s):

Free Energy ◽

Lipid Membranes ◽

Energy Landscape ◽

Reaction Coordinate ◽

Free Energy Landscape ◽

Pore Nucleation ◽

Joint Reaction ◽

Pore Expansion

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Location-thinking, value-thinking, and graphical forms: combining analytical frameworks to analyze inferences made by students when interpreting the points and trends on a reaction coordinate diagram

Chemistry Education Research and Practice ◽

10.1039/d1rp00037c ◽

2021 ◽

Author(s):

Alexander P. Parobek ◽

Patrick M. Chaffin ◽

Marcy H. Towns

Keyword(s):

Reaction Rate ◽

Research Study ◽

Reaction Rates ◽

Reaction Coordinate ◽

Structured Interviews ◽

Chemistry Students ◽

Qualitative Research Study ◽

The Impact ◽

Analytical Frameworks ◽

Chemical Representations

Reaction coordinate diagrams (RCDs) are chemical representations widely employed to visualize the thermodynamic and kinetic parameters associated with reactions. Previous research has demonstrated a host of misconceptions students adopt when interpreting the perceived information encoded in RCDs. This qualitative research study explores how general chemistry students interpret points and trends on a RCD and how these interpretations impact their inferences regarding the rate of a chemical reaction. Sixteen students participated in semi-structured interviews in which participants were asked to interpret the points and trends along provided RCDs and to compare relative reaction rates between RCDs. Findings derived from this study demonstrate the diversity of graphical reasoning adopted by students, the impact of students’ interpretations of the x-axis of a RCD on the graphical reasoning employed, and the influence of these ideas on inferences made about reaction rate. Informed by analytical frameworks grounded in the resources framework and the actor-oriented model of transfer, implications for instruction are provided with suggestions for how RCDs may be presented to assist students in recognizing the critical information encoded in these diagrams.

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Spontaneous and frequent conformational dynamics induced by A…A mismatch in d(CAA)·d(TAG) duplex

Scientific Reports ◽

10.1038/s41598-021-82669-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yogeeshwar Ajjugal ◽

Kripi Tomar ◽

D. Krishna Rao ◽

Thenmalarchelvi Rathinavelan

Keyword(s):

Mismatch Repair ◽

Conformational Dynamics ◽

Md Simulations ◽

Umbrella Sampling ◽

Base Flipping ◽

Base Pairs ◽

2D Noesy ◽

Junction Formation ◽

Nmr Techniques ◽

Transient Events

AbstractBase pair mismatches in DNA can erroneously be incorporated during replication, recombination, etc. Here, the influence of A…A mismatch in the context of 5′CAA·5′TAG sequence is explored using molecular dynamics (MD) simulation, umbrella sampling MD, circular dichroism (CD), microscale thermophoresis (MST) and NMR techniques. MD simulations reveal that the A…A mismatch experiences several transient events such as base flipping, base extrusion, etc. facilitating B–Z junction formation. A…A mismatch may assume such conformational transitions to circumvent the effect of nonisostericity with the flanking canonical base pairs so as to get accommodated in the DNA. CD and 1D proton NMR experiments further reveal that the extent of B–Z junction increases when the number of A…A mismatch in d(CAA)·d(T(A/T)G) increases (1–5). CD titration studies of d(CAA)·d(TAG)n=5 with the hZαADAR1 show the passive binding between the two, wherein, the binding of protein commences with B–Z junction recognition. Umbrella sampling simulation indicates that the mismatch samples anti…+ syn/+ syn…anti, anti…anti & + syn…+ syn glycosyl conformations. The concomitant spontaneous transitions are: a variety of hydrogen bonding patterns, stacking and minor or major groove extrahelical movements (with and without the engagement of hydrogen bonds) involving the mismatch adenines. These transitions frequently happen in anti…anti conformational region compared with the other three regions as revealed from the lifetime of these states. Further, 2D-NOESY experiments indicate that the number of cross-peaks diminishes with the increasing number of A…A mismatches implicating its dynamic nature. The spontaneous extrahelical movement seen in A…A mismatch may be a key pre-trapping event in the mismatch repair due to the accessibility of the base(s) to the sophisticated mismatch repair machinery.

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Measuring Changes in Undergraduate Chemistry Students’ Reasoning with Reaction Coordinate Diagrams: A Longitudinal, Multi-institution Study

Journal of Chemical Education ◽

10.1021/acs.jchemed.0c01419 ◽

2021 ◽

Vol 98 (4) ◽

pp. 1064-1076

Author(s):

Molly B. Atkinson ◽

Stacey Lowery Bretz

Keyword(s):

Reaction Coordinate ◽

Chemistry Students ◽

Undergraduate Chemistry

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On the 3D → 2D Isomerization of Hexaborane(12)

Chemistry ◽

10.3390/chemistry3010003 ◽

2021 ◽

Vol 3 (1) ◽

pp. 28-38

Author(s):

Josep M. Oliva-Enrich ◽

Ibon Alkorta ◽

José Elguero ◽

Maxime Ferrer ◽

José I. Burgos

Keyword(s):

Potential Energy ◽

Potential Energy Surface ◽

Energy Surface ◽

Transition States ◽

Three Dimensional ◽

Reaction Coordinate ◽

Intrinsic Reaction Coordinate ◽

Limiting Factor ◽

Two Dimensional ◽

Axis Of Rotation

By following the intrinsic reaction coordinate connecting transition states with energy minima on the potential energy surface, we have determined the reaction steps connecting three-dimensional hexaborane(12) with unknown planar two-dimensional hexaborane(12). In an effort to predict the potential synthesis of finite planar borane molecules, we found that the reaction limiting factor stems from the breaking of the central boron-boron bond perpendicular to the C2 axis of rotation in three-dimensional hexaborane(12).

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