Quantitative Assessment of the Interplay Between DNA Elasticity and Cooperative Binding of Ligands

Siman, Lívia; Carrasco, I. S. S.; Silva, J. Kamphorst Leal da; Oliveira, Maria Cristina de; Rocha, M. S.; Mesquita, O. N.

doi:10.1103/physrevlett.109.248103

Cited by 44 publications

(69 citation statements)

References 13 publications

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“…Basically the model introduces the Hill exponent n, a cooperativity parameter which is a lower bound for the number of cooperating ligand molecules involved in the reaction 63,64 . The binding isotherm reads…”

Section: B Scatchard Modelmentioning

confidence: 99%

“…Along the past years many groups have used single molecule techniques to identify the possible binding mechanisms of DNA-ligand interactions and to extract physicochemical information of such interactions from these types of experiments 56,63,65,75,[90][91][92]97,98,137,140,158,[165][166][167][168][169][170][171][172] .…”

Section: A Historical Surveymentioning

confidence: 99%

“…We have found the results K i = (9 ± 1) × 10 4 M −1 , n = 3.7 ± 0.4, A 1 = (8.4 ± 1) nm and A 2 = (149 ± 21) nm. The parameter r max = 0.67 was known for this ligand such that we have fixed its value in the fitting 63 . The value obtained for the Hill exponent n again indicates that the system is positively cooperative, in this case forming bound clusters of ∼ 4 drug molecules at the binding sites 63 .…”

Section: B a General Model To Connect The Persistence Length To Physmentioning

confidence: 99%

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Extracting physical chemistry from mechanics: a new approach to investigate DNA interactions with drugs and proteins in single molecule experiments

Rocha

2015

Integr. Biol.

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116

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In this review we focus on the idea of establishing connections between the mechanical properties of DNAligand complexes and the physical chemistry of DNA-ligand interactions. This type of connection is interesting because it opens the possibility of performing a robust characterization of such interactions by using only one experimental technique: single molecule stretching. Furthermore, it also opens new possibilities in comparing results obtained by very different approaches, in special when comparing single molecule techniques to ensemble-averaging techniques. We start the manuscript reviewing important concepts of the DNA mechanics, from the basic mechanical properties to the Worm-Like Chain model. Next we review the basic concepts of the physical chemistry of DNA-ligand interactions, revisiting the most important models used to analyze the binding data and discussing their binding isotherms. Then, we discuss the basic features of the single molecule techniques most used to stretch the DNA-ligand complexes and to obtain force × extension data, from which the mechanical properties of the complexes can be determined. We also discuss the characteristics of the main types of interactions that can occur between DNA and ligands, from covalent binding to simple electrostatic driven interactions. Finally, we present a historical survey on the attempts to connect mechanics to physical chemistry for DNA-ligand systems, emphasizing a recently developed fitting approach useful to connect the persistence length of the DNA-ligand complexes to the physicochemical properties of the interaction. Such approach in principle can be used for any type of ligand, from drugs to proteins, even if multiple binding modes are present.

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Section: B Scatchard Modelmentioning

confidence: 99%

Section: A Historical Surveymentioning

confidence: 99%

Section: B a General Model To Connect The Persistence Length To Physmentioning

confidence: 99%

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Extracting physical chemistry from mechanics: a new approach to investigate DNA interactions with drugs and proteins in single molecule experiments

Rocha

2015

Integr. Biol.

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116

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“…Interestingly, the extent of complexation depends significantly on the base composition and the doubleor triple-helical structures. In contrast to native CDs, cationic CDs are known to interact strongly with DNA [109,110]. As consequence, CDs can be used to complex DNA and to encapsulate it into liposomes for potential gene therapy applications [111].…”

Section: Iv) Complexation Of Nucleic Acidsmentioning

confidence: 99%

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

Leclercq¹

2016

Beilstein J. Org. Chem.

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In the field of host–guest chemistry, some of the most widely used hosts are probably cyclodextrins (CDs). As CDs are able to increase the water solubility of numerous drugs by inclusion into their hydrophobic cavity, they have been widespread used to develop numerous pharmaceutical formulations. Nevertheless, CDs are also able to interact with endogenous substances that originate from an organism, tissue or cell. These interactions can be useful for a vast array of topics including cholesterol manipulation, treatment of Alzheimer’s disease, control of pathogens, etc. In addition, the use of natural CDs offers the great advantage of avoiding or reducing the use of common petroleum-sourced drugs. In this paper, the general features and applications of CDs have been reviewed as well as their interactions with isolated biomolecules leading to the formation of inclusion or exclusion complexes. Finally, some potential medical applications are highlighted throughout several examples.

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“…4 unless the possibility is considered that the cell has other mechanisms for influencing q el and q ad . DNA interacts with other cellular components which can modify the q ad or q el [67][68][69][70]. Either type of interaction will affect q net , perhaps to the point of favoring DNA-histone separation rather than binding.…”

Section: B Rough Binding Energy Landscapementioning

confidence: 99%

DNA damage may drive nucleosomal reorganization to facilitate damage detection

2014

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One issue in genome maintenance is how DNA repair proteins find lesions at rates that seem to exceed diffusion-limited search rates. We propose a phenomenon where DNA damage induces nucleosomal rearrangements which move lesions to potential rendezvous points in the chromatin structure. These rendezvous points are the dyad and the linker DNA between histones, positions in the chromatin which are more likely to be accessible by repair proteins engaged in a random search. The feasibility of this mechanism is tested by considering the statistical mechanics of DNA containing a single lesion wrapped onto the nucleosome. We consider lesions which make the DNA either more flexible or more rigid by modeling the lesion as either a decrease or an increase in the bending energy. We include this energy in a partition function model of nucleosome breathing. Our results indicate that the steady state for a breathing nucleosome will most likely position the lesion at the dyad or in the linker, depending on the energy of the lesion. A role for DNA binding proteins and chromatin remodelers is suggested based on their ability to alter the mechanical properties of the DNA and DNA-histone binding, respectively. We speculate that these positions around the nucleosome potentially serve as rendezvous points where DNA lesions may be encountered by repair proteins which may be sterically hindered from searching the rest of the nucleosomal DNA. The strength of the repositioning is strongly dependent on the structural details of the DNA lesion and the wrapping and breathing of the nucleosome. A more sophisticated evaluation of this proposed mechanism will require detailed information about breathing dynamics, the structure of partially wrapped nucleosomes, and the structural properties of damaged DNA.

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Quantitative Assessment of the Interplay Between DNA Elasticity and Cooperative Binding of Ligands

Cited by 44 publications

References 13 publications

Extracting physical chemistry from mechanics: a new approach to investigate DNA interactions with drugs and proteins in single molecule experiments

Extracting physical chemistry from mechanics: a new approach to investigate DNA interactions with drugs and proteins in single molecule experiments

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

DNA damage may drive nucleosomal reorganization to facilitate damage detection

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