scholarly journals Exploring the Binding Mechanism and Dynamics of EndoMS/NucS to Mismatched dsDNA

2019 ◽  
Vol 20 (20) ◽  
pp. 5142
Author(s):  
Yanjun Zhang ◽  
Shengyou Huang
Keyword(s):  
Mismatch Repair ◽  
Md Simulations ◽  
Repair Process ◽  
Energy Curve ◽  
Energy Minimum ◽  
Recognition Mechanism ◽  
Local Energy Minimum ◽  
Closed State ◽  
Global Energy Minimum ◽  
Terminal Domains

The well-known mismatch repair (MMR) machinery, MutS/MutL, is absent in numerous Archaea and some Bacteria. Recent studies have shown that EndoMS/NucS has the ability to cleave double-stranded DNA (dsDNA) containing a mismatched base pair, which suggests a novel mismatch repair process. However, the recognition mechanism and the binding process of EndoMS/NucS in the MMR pathway remain unclear. In this study, we investigate the binding dynamics of EndoMS/NucS to mismatched dsDNA and its energy as a function of the angle between the two C-terminal domains of EndoMS/NucS, through molecular docking and extensive molecular dynamics (MD) simulations. It is found that there exists a half-open transition state corresponding to an energy barrier (at an activation angle of approximately 80 ∘ ) between the open state and the closed state, according to the energy curve. When the angle is larger than the activation angle, the C-terminal domains can move freely and tend to change to the open state (local energy minimum). Otherwise, the C-terminal domains will interact with the mismatched dsDNA directly and converge to the closed state at the global energy minimum. As such, this two-state system enables the exposed N-terminal domains of EndoMS/NucS to recognize mismatched dsDNA during the open state and then stabilize the binding of the C-terminal domains of EndoMS/NucS to the mismatched dsDNA during the closed state. We also investigate how the EndoMS/NucS recognizes and binds to mismatched dsDNA, as well as the effects of K + ions. The results provide insights into the recognition and binding mechanisms of EndoMS/NucS to mismatched dsDNA in the MMR pathway.

p-WAVE PAIRING IN FERMI SYSTEMS WITH UNEQUAL POPULATION NEAR FESHBACH RESONANCE

2008 ◽  
Vol 22 (25n26) ◽  
pp. 4358-4366 ◽  
Author(s):  
KHANDKER F. QUADER ◽  
RENYUAN LIAO ◽  
FLORENTIN POPESCU
Keyword(s):  
Feshbach Resonance ◽  
Single Channel ◽  
Numerical Study ◽  
Fermi System ◽  
P Wave ◽  
Ground State Structure ◽  
Energy Minimum ◽  
Local Energy Minimum ◽  
Wave Pairing ◽  
Global Energy Minimum

We explore p-wave pairing in a single-channel two-component Fermi system with unequal population near Feshbach resonance. Our analytical and numerical study reveal a rich superfluid (SF) ground state structure as a function of imbalance. In addition to the state Δ±1 ∝ Y1±1, a multitude of “mixed” SF states formed of linear combinations of Y1m's give global energy minimum under a phase stability condition; these states exhibit variation in energy with the relative phase between the constituent gap amplitudes. States with local energy minimum are also obtained. We provide a geometric representation of the states. A T = 0 polarization vs. p-wave coupling phase diagram is constructed across the BEC-BCS regimes. With increased polarization, the global minimum SF state may undergo a quantum phase transition to the local minimum SF state.

scholarly journals Binding of HasA by its transmembrane receptor HasR follows a conformational funnel mechanism

2019 ◽  
Vol 49 (1) ◽  
pp. 39-57
Author(s):  
Thomas E. Exner ◽  
Stefanie Becker ◽  
Simon Becker ◽  
Audrey Boniface-Guiraud ◽  
Philippe Delepelaire ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Specific Binding ◽  
Md Simulations ◽  
Energy Minimum ◽  
Wild Type ◽  
Double Mutation ◽  
Starting Position ◽  
Local Energy Minimum ◽  
Type Complex ◽  
Heme Transfer

AbstractHasR in the outer membrane of Serratia marcescens binds secreted, heme-loaded HasA and translocates the heme to the periplasm to satisfy the cell’s demand for iron. The previously published crystal structure of the wild-type complex showed HasA in a very specific binding arrangement with HasR, apt to relax the grasp on the heme and assure its directed transfer to the HasR-binding site. Here, we present a new crystal structure of the heme-loaded HasA arranged with a mutant of HasR, called double mutant (DM) in the following that seemed to mimic a precursor stage of the abovementioned final arrangement before heme transfer. To test this, we performed first molecular dynamics (MD) simulations starting at the crystal structure of the complex of HasA with the DM mutant and then targeted MD simulations of the entire binding process beginning with heme-loaded HasA in solution. When the simulation starts with the former complex, the two proteins in most simulations do not dissociate. When the mutations are reverted to the wild-type sequence, dissociation and development toward the wild-type complex occur in most simulations. This indicates that the mutations create or enhance a local energy minimum. In the targeted MD simulations, the first protein contacts depend upon the chosen starting position of HasA in solution. Subsequently, heme-loaded HasA slides on the external surface of HasR on paths that converge toward the specific arrangement apt for heme transfer. The targeted simulations end when HasR starts to relax the grasp on the heme, the subsequent events being in a time regime inaccessible to the available computing power. Interestingly, none of the ten independent simulation paths visits exactly the arrangement of HasA with HasR seen in the crystal structure of the mutant. Two factors which do not exclude each other could explain these observations: the double mutation creates a non-physiologic potential energy minimum between the two proteins and /or the target potential in the simulation pushes the system along paths deviating from the low-energy paths of the native binding processes. Our results support the former view, but do not exclude the latter possibility.

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

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.

Comprehensive Global Energy Minimum Modeling of the Sarin−Serine Adduct

2005 ◽  
Vol 109 (2) ◽  
pp. 1006-1014 ◽  
Author(s):  
Jing Wang ◽  
Szczepan Roszak ◽  
Jiande Gu ◽  
Jerzy Leszczynski
Keyword(s):  
Energy Minimum ◽  
Global Energy ◽  
Global Energy Minimum

scholarly journals Modern Aspects of the Structural and Functional Organization of the DNA Mismatch Repair System

Acta Naturae ◽  
2013 ◽  
Vol 5 (3) ◽  
pp. 17-34 ◽  
Author(s):  
S. A. Perevoztchikova ◽  
E. A. Romanova ◽  
T. S. Oretskaya ◽  
P. Friedhoff ◽  
E. A. Kubareva
Keyword(s):  
Mismatch Repair ◽  
Functional Organization ◽  
Dna Mismatch Repair ◽  
Repair Process ◽  
Repair System ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System ◽  
General Aspects ◽  
The Relationship

This review is focused on the general aspects of the DNA mismatch repair (MMR) process. The key proteins of the DNA mismatch repair system are MutS and MutL. To date, their main structural and functional characteristics have been thoroughly studied. However, different opinions exist about the initial stages of the mismatch repair process with the participation of these proteins. This review aims to summarize the data on the relationship between the two MutS functions, ATPase and DNA-binding, and to systematize various models of coordination between the mismatch site and the strand discrimination site in DNA. To test these models, novel techniques for the trapping of short-living complexes that appear at different MMR stages are to be developed.

scholarly journals Mechanism and Control of Interspecies Recombination in Escherichia coli. I. Mismatch Repair, Methylation, Recombination and Replication Functions

Genetics ◽  
1998 ◽  
Vol 150 (2) ◽  
pp. 533-542 ◽  
Author(s):  
Snježana Štambuk ◽  
Miroslav Radman
Keyword(s):  
Escherichia Coli ◽  
Mismatch Repair ◽  
Dna Sequences ◽  
Sequence Divergence ◽  
Repair Process ◽  
Helicase Activity ◽  
Dam Methylation ◽  
Homeologous Recombination ◽  
And Control ◽  
Interspecies Recombination

Abstract A genetic analysis of interspecies recombination in Escherichia coli between the linear Hfr DNA from Salmonella typhimurium and the circular recipient chromosome reveals some fundamental aspects of recombination between related DNA sequences. The MutS and MutL mismatch binding proteins edit (prevent) homeologous recombination between these 16% diverged genomes by at least two distinct mechanisms. One is MutH independent and presumably acts by aborting the initiated recombination through the UvrD helicase activity. The RecBCD nuclease might contribute to this editing step, presumably by preventing reiterated initiations of recombination at a given locus. The other editing mechanism is MutH dependent, requires unmethylated GATC sequences, and probably corresponds to an incomplete long-patch mismatch repair process that does not depend on UvrD helicase activity. Insignificant effects of the Dam methylation of parental DNAs suggest that unmethylated GATC sequences involved in the MutH-dependent editing are newly synthesized in the course of recombination. This hypothetical, recombination-associated DNA synthesis involves PriA and RecF functions, which, therefore, determine the extent of MutH effect on interspecies recombination. Sequence divergence of recombining DNAs appears to limit the frequency, length, and stability of early heteroduplex intermediates, which can be stabilized, and the recombinants mature via the initiation of DNA replication.

scholarly journals Sulphur-Bridged BAl5S5+ with 17 Counting Electrons: A Regular Planar Pentacoordinate Boron System

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5205
Author(s):  
Yuhan Ye ◽  
Yiqiao Wang ◽  
Min Zhang ◽  
Yun Geng ◽  
Zhongmin Su
Keyword(s):  
Particle Swarm Optimization ◽  
Chemical Bonding ◽  
Theoretical Basis ◽  
Optimization Method ◽  
Energy Minimum ◽  
Swarm Optimization ◽  
Bonding Analysis ◽  
Global Energy Minimum ◽  
Star Configuration ◽  
Pointed Star

At present, most of the reported planar pentacoordinate clusters are similar to the isoelectronic substitution of CAl5+, with 18 counting electrons. Meanwhile, the regular planar pentacoordinate boron systems are rarely reported. Hereby, a sulphur-bridged BAl5S5+ system with a five-pointed star configuration and 17 counting electrons is identified at the global energy minimum through the particle-swarm optimization method, based on the previous recognition on bridged sulphur as the peripheral tactics to the stable planar tetracoordinate carbon and boron. Its outstanding stability has been demonstrated by thermodynamic analysis at 900 K, electronic properties and chemical bonding analysis. This study provides adequately theoretical basis and referable data for its experimental capture and testing.

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