A hydrophobic similarity analysis of solvation effects on nucleic acid bases

Munoz-Muriedas, Jordi; Barril, Xavier; López, José María Botana; Orozco, Modesto; Luque, F. Javier

doi:10.1007/s00894-006-0150-y

Cited by 8 publications

(10 citation statements)

References 65 publications

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“…For d w < 0.9 nm, dAMP, dCMP, and dTMP had minima in θ for both adsorption and desorption, indicating that the sugar adsorbed after the nucleobase and desorbed before the nucleobase. The magnitude of the minima of θ followed the order dCMP < dAMP < dTMP, which was consistent with the order of hydrophobicity of their nucleobases. , For d w < 0.9 nm, dGMP had a maximum in θ for both adsorption and desorption, indicating that the sugar adsorbed before the nucleobase and desorbed after the nucleobase. The different behavior of dGMP was likely because its nucleobase was the least hydrophobic. , The adsorption and desorption curves for each type of dNMP were similar to each other which indicated that adsorption and desorption occurred in a similar way.…”

Section: Results and Discussionsupporting

confidence: 70%

“…The different behavior of dGMP was likely because its nucleobase was the least hydrophobic. 67, 68 The adsorption and desorption curves for each type of dNMP were similar to each other which indicated that adsorption and desorption occurred in a similar way.…”

Section: Thementioning

confidence: 75%

“…The trend in the velocities while adsorbed was dTMP > dCMP ≈ dGMP > dAMP (see Figure b), but if this simple explanation were true, then the expected order would be dCMP > dTMP > dAMP > dGMP. The most important additional factor was the fraction of time adsorbed (see Figure a) which was related to the hydrophobicity of the dNMP nucleobases. , dTMP was more hydrophobic than dCMP and spent a much larger fraction of time adsorbed than dCMP, so its overall velocity was lower than that for dCMP even though it moved faster than dCMP while adsorbed. A similar argument holds for dGMP and dAMP; dAMP was more hydrophobic leading to a swapping in the order of their overall velocities compared to their velocities while adsorbed.…”

Section: Results and Discussionmentioning

confidence: 99%

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Electrophoretic Transport of Single DNA Nucleotides through Nanoslits: A Molecular Dynamics Simulation Study

et al. 2015

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There is potential for flight time based DNA sequencing involving disassembly into individual nucleotides which would pass through a nanochannel with two or more detectors. We performed molecular dynamics simulations of electrophoretic motion of single DNA nucleotides through 3 nm wide hydrophobic slits with both smooth and rough walls. The electric field (E) varied from 0.0 to 0.6 V/nm. The nucleotides adsorb and desorb from walls multiple times during their transit through the slit. The nucleotide-wall interactions differed due to nucleotide hydrophobicities and wall roughness which determined duration and frequency of nucleotide adsorptions and their velocities while adsorbed. Transient association of nucleotides with one, two, or three sodium ions occurred, but the mean association numbers (ANs) were weak functions of nucleotide type. Nucleotide-wall interactions contributed more to separation of nucleotide flight time distributions than ion association and thus indicate that nucleotide-wall interactions play a defining role in successfully discriminating between nucleotides on the basis of their flight times through nanochannels/slits. With smooth walls, smaller nucleotides moved faster, but with rough walls larger nucleotides moved faster due to fewer favorable wall adsorption sites. This indicates that roughness, or surface patterning, might be exploited to achieve better time-of-flight based discrimination between nucleotides.

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Section: Results and Discussionsupporting

confidence: 70%

Section: Thementioning

confidence: 75%

Section: Results and Discussionmentioning

confidence: 99%

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Electrophoretic Transport of Single DNA Nucleotides through Nanoslits: A Molecular Dynamics Simulation Study

et al. 2015

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“…QM-based continuum solvation methods are a promising strategy for deriving 3D descriptors, such as COSMO-RS-based σ-profiles [78][79][80][81] or MST-derived 3D lipophilicity patterns [82][83][84][97][98][99], which in turn may be exploited in computer-aided drug design. The set of studies reported up to now for a variety of benchmark datasets, covering both measurements of molecular similarity for aligned compound or the derivation of 3D-QSAR models, are encouraging.…”

Section: Final Consideration and Perspectivesmentioning

confidence: 99%

Lipophilicity in Drug Design: An Overview of Lipophilicity Descriptors in 3D-QSAR Studies

Ginex

Vázquez

Gilbert³

et al. 2019

Future Med. Chem.

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The pharmacophore concept is a fundamental cornerstone in drug discovery, playing a critical role in determining the success of in silico techniques, such as virtual screening and 3D-QSAR studies. The reliability of these approaches is influenced by the quality of the physicochemical descriptors used to characterize the chemical entities. In this context, a pivotal role is exerted by lipophilicity, which is a major contribution to host-guest interaction and ligand binding affinity. Several approaches have been undertaken to account for the descriptive and predictive capabilities of lipophilicity in 3D-QSAR modelling. Recent efforts encode the use of quantum mechanical-based descriptors derived from continuum solvation models, which open novel avenues for gaining insight into structure-activity relationships studies.

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“…In this work, following our previous studies on hydrophobic similarity, the QM/MST‐based hydrophobic contributions have been utilized as physicochemical descriptors suitable for 3D‐QSAR studies. By combining the electrostatic and nonelectrostatic components of the octanol/water partition coefficient, which can obtained through a suitable partitioning of the solvation free energy, the 3D‐QSAR models derived for the five molecular systems have a predictive accuracy that compares well with standard CoMFA and CoMSIA techniques.…”

Section: Final Remarksmentioning

confidence: 99%

Development and validation of hydrophobic molecular fields derived from the quantum mechanical IEF/PCM‐MST solvation models in 3D‐QSAR

et al. 2016

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Since the development of structure-activity relationships about 50 years ago, 3D-QSAR methods belong to the most refined ligand-based in silico techniques for prediction of biological data using physicochemical molecular fields. In this scenario, this study reports the development and validation of quantum mechanical (QM)-based hydrophobic descriptors derived from the parametrized MST continuum solvation model to be used in 3D-QSAR studies within the framework of the Hydrophobic Pharmacophore (HyPhar) method. To this end, five sets of compounds reported in the literature (dopamine D2/D4 antagonists, antifungal 2-aryl-4-chromanones, and inhibitors of GSK-3, cruzain and thermolysin) have been revisited. The results derived from the QM/MST-based hydrophobic descriptors have been compared with previous CoMFA and CoMSIA studies, and examined in light of the available X-ray crystallographic structures of the targets. The analysis reveals that the combination of electrostatic and nonelectrostatic components of the octanol/water partition coefficient yields pharmacophoric models fully comparable with the predictive potential of standard 3D-QSAR techniques. Moreover, the graphical representation of the hydrophobic maps provides a direct linkage with the pattern of interactions found in crystallographic structures. Overall, the introduction of the QM/MST-based descriptors, which could be easily adapted to other continuum solvation formalisms, paves the way to novel computational strategies for disclosing structure-activity relationships in drug design. © 2016 Wiley Periodicals, Inc.

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A hydrophobic similarity analysis of solvation effects on nucleic acid bases

Cited by 8 publications

References 65 publications

Electrophoretic Transport of Single DNA Nucleotides through Nanoslits: A Molecular Dynamics Simulation Study

Electrophoretic Transport of Single DNA Nucleotides through Nanoslits: A Molecular Dynamics Simulation Study

Lipophilicity in Drug Design: An Overview of Lipophilicity Descriptors in 3D-QSAR Studies

Development and validation of hydrophobic molecular fields derived from the quantum mechanical IEF/PCM‐MST solvation models in 3D‐QSAR

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