Simulation of dissociation of DNA duplexes attached to the surface

Open Physics ◽  
2010 ◽  
Vol 8 (6) ◽  
Author(s):  
Vladimir Zhdanov ◽  
Anders Gunnarsson ◽  
Fredrik Höök
Keyword(s):  
Surface Heterogeneity ◽  
Bound State ◽  
Coarse Grained ◽  
Dna Duplexes ◽  
Extrinsic Factors ◽  
Coarse Grained Model ◽  
Dna Base ◽  
Dna Base Pair ◽  
Complete Dissociation ◽  
And Diffusion

AbstractWe present Monte Carlo simulations of dissociation of duplexes formed of complementary single-stranded DNAs with one of the strands attached to the surface. To describe the transition from the bound state to the unbound state of two strands located nearby, we use a lattice model taking DNA base-pair interactions and comformational changes into account. The results obtained are employed as a basis for a more coarse-grained model including strand backward association and diffusion resulting in complete dissociation. The distribution of the dissociation time is found to be exponential. This finding indicates that the non-exponential kinetic features observed in the corresponding experiments seem to be related to extrinsic factors, e.g., to the surface heterogeneity.

scholarly journals Self-assembly of short DNA duplexes: from a coarse-grained model to experiments through a theoretical link

Soft Matter ◽  
2012 ◽  
Vol 8 (32) ◽  
pp. 8388 ◽  
Author(s):  
Cristiano De Michele ◽  
Lorenzo Rovigatti ◽  
Tommaso Bellini ◽  
Francesco Sciortino
Keyword(s):  
Self Assembly ◽  
Coarse Grained ◽  
Dna Duplexes ◽  
Coarse Grained Model

scholarly journals Coarse-grained molecular simulations of the binding of the SARS-CoV-2 spike protein RBD to the ACE2 receptor

2020 ◽  
Author(s):  
David De Sancho ◽  
José A. Gavira ◽  
Raul Pérez-Jiménez
Keyword(s):  
Bound States ◽  
Dynamic Behaviour ◽  
Molecular Level ◽  
Molecular Simulations ◽  
Bound State ◽  
Spike Protein ◽  
Coarse Grained ◽  
Receptor Binding Domain ◽  
Coarse Grained Model ◽  
Dynamic Description

AbstractSince it was first observed, the COVID-19 pandemic has created a global emergency for national health systems due to millions of confirmed cases and hundreds of thousands of deaths. At a molecular level, the bottleneck for the infection is the binding of the receptor binding domain (RBD) of the viral spike protein to ACE2, an enzyme exposed on human cell membranes. Several experimental structures of the ACE2:RBD complex have been made available, however they offer only a static description of the arrangements of the molecules in either the free or bound states. In order to gain a dynamic description of the binding process that is key to infection, we use molecular simulations with a coarse grained model of the RBD and ACE2. We find that binding occurs in an all-or-none way, without intermediates, and that even in the bound state, the RBD exhibits a considerably dynamic behaviour. From short equilibrium simulations started in the unbound state we provide snapshots that result in a tentative mechanism of binding. Our findings may be important for the development of drug discovery strategies that target the RBD.

SCREW MOTION OF DNA DUPLEX DURING TRANSLOCATION THROUGH PORE I: INTRODUCTION OF THE COARSE-GRAINED MODEL

2009 ◽  
Vol 04 (03) ◽  
pp. 209-230 ◽  
Author(s):  
E. B. STARIKOV ◽  
D. HENNIG ◽  
H. YAMADA ◽  
R. GUTIERREZ ◽  
B. NORDÉN ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Mechanical Energy ◽  
Hydration Shell ◽  
Electrical Potential ◽  
Electrical Current ◽  
Coarse Grained ◽  
Dna Duplexes ◽  
Coarse Grained Model ◽  
Analogous Model ◽  
Pair Sequence

Based upon the structural properties of DNA duplexes and their counterion-water surrounding in solution, we have introduced here a screw model which may describe translocation of DNA duplexes through artificial nanopores of the proper diameter (where the DNA counterion–hydration shell can be intact) in a qualitatively correct way. This model represents DNA as a kind of "screw," whereas the counterion-hydration shell is a kind of "nut." Mathematical conditions for stable dynamics of the DNA screw model are investigated in detail. When an electrical potential is applied across an artificial membrane with a nanopore, the "screw" and "nut" begin to move with respect to each other, so that their mutual rotation is coupled with their mutual translation. As a result, there are peaks of electrical current connected with the mutual translocation of DNA and its counterion–hydration shell, if DNA is possessed of some non-regular base-pair sequence. The calculated peaks of current strongly resemble those observed in the pertinent experiments. An analogous model could in principle be applied to DNA translocation in natural DNA–protein complexes of biological interest, where the role of "nut" would be played by protein-tailored "channels." In such cases, the DNA screw model is capable of qualitatively explaining chemical-to-mechanical energy conversion in DNA–protein molecular machines via symmetry breaking in DNA–protein friction.

Insights Into Crowding Effects on Protein Stability From a Coarse-Grained Model

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
Vincent K. Shen ◽  
Jason K. Cheung ◽  
Jeffrey R. Errington ◽  
Thomas M. Truskett
Keyword(s):  
Protein Stability ◽  
Coarse Grained ◽  
Protein Solutions ◽  
Native State ◽  
High Concentration ◽  
Coarse Grained Model ◽  
Excluded Volume Effects ◽  
Thermodynamic Phase ◽  
Broad Interest ◽  
Liquid Liquid Phase Separation

Proteins aggregate and precipitate from high concentration solutions in a wide variety of problems of natural and technological interest. Consequently, there is a broad interest in developing new ways to model the thermodynamic and kinetic aspects of protein stability in these crowded cellular or solution environments. We use a coarse-grained modeling approach to study the effects of different crowding agents on the conformational equilibria of proteins and the thermodynamic phase behavior of their solutions. At low to moderate protein concentrations, we find that crowding species can either stabilize or destabilize the native state, depending on the strength of their attractive interaction with the proteins. At high protein concentrations, crowders tend to stabilize the native state due to excluded volume effects, irrespective of the strength of the crowder-protein attraction. Crowding agents reduce the tendency of protein solutions to undergo a liquid-liquid phase separation driven by strong protein-protein attractions. The aforementioned equilibrium trends represent, to our knowledge, the first simulation predictions for how the properties of crowding species impact the global thermodynamic stability of proteins and their solutions.

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