A DNA intercalation methodology for an efficient prediction of ligand binding pose and energetics

Soni, Anjali; Khurana, Pooja; Singh, Tanya; Jayaram, B.

doi:10.1093/bioinformatics/btx006

Cited by 41 publications

(30 citation statements)

References 68 publications

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“…Drug -DNA intercalation is often employed in cancer therapies. AutoDock was able to successfully distinguish between the intercalation site and the minor-groove site and reproduce the binding mode within 2 Å with a success rate of 80% (a datasete of 67 DNA-intercalator complexes) [70,71] By using DNA sequence and intercalation site information, a novel intercalation methodology called 'Intercalate' was able to create the DNA 3D structure with the intercalation site and perform docking at the binding site with associate binding free energies [72].…”

Section: Prediction Of Binding Modesmentioning

confidence: 99%

Challenges and current status of computational methods for docking small molecules to nucleic acids

Luo

Wei

Waldispühl

et al. 2019

European Journal of Medicinal Chemistry

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Since the development of the first docking program in 1982, their use in in silico screening for potentially bioactive molecule discovery has become a common strategy in academia and pharmaceutical industry. Up until recently, their use has largely focused on drugs binding to proteins. However, with the relatively recent discovery of promising drug targets in nucleic acids, including RNA riboswitches, DNA G-quadruplexes, and extended repeats in RNA, there has been a greater interest in developing drugs for nucleic acids. However, due to the major biochemical and physical differences in charges, binding pockets, and solvation, existing docking programs, developed for proteins, face difficulties when adopted directly for nucleic acids. In this review, we cover the current field of in silico docking to nucleic acids, available programs, as well as challenges faced in the field.

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Section: Prediction Of Binding Modesmentioning

confidence: 99%

Challenges and current status of computational methods for docking small molecules to nucleic acids

Luo

Wei

Waldispühl

et al. 2019

European Journal of Medicinal Chemistry

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show abstract

“…In other words, a docking procedure can only provide a possible interaction geometry but is not suitable for assessing the binding energetics. For this purpose, other contributions would have to be considered, including deformation energy of DNA unwinding, counterion effects, desolvation, and entropy 8 . Therefore, the conclusion that “the docking results supported the presence of intercalative mode of binding between SIL and ctDNA” is unfounded and is most probably wrong.…”

Section: Concerns In Computational Chemistry and Electrochemistry Partsmentioning

confidence: 99%

Flavonolignans from silymarin do not intercalate intoDNA: Rebuttal of data published in the paperJ. Mol. Recognit. e2812 (2019)

Biedermann

Hurtová

Biedermannová

et al. 2021

J of Molecular Recognition

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“…The unique features of DNA in comparison to proteins or peptides make it difficult to apply existing computational drug discovery tools to DNA. This is due in part to the inability of standard docking protocols and MM potentials to provide reliable intercalation binding energies . One route to improving such tools is through parameterization based on reliable quantum mechanical (QM) computations.…”

Section: Introductionmentioning

confidence: 99%

“…This is due in part to the inability of standard docking protocols and MM potentials to provide reliable intercalation binding energies. [6][7][8] One route to improving such tools is through parameterization based on reliable quantum mechanical (QM) computations. However, this requires that a sufficiently reliable yet computationally tractable QM method be identified.…”

mentioning

confidence: 99%

Importance of model size in quantum mechanical studies of DNA intercalation

et al. 2020

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The convergence of DFT‐computed interaction energies with increasing binding site model size was assessed. The data show that while accurate intercalator interaction energies can be derived from binding site models featuring only the flanking nucleotides for uncharged intercalators that bind parallel to the DNA base pairs, errors remain significant even when including distant nucleotides for intercalators that are charged, exhibit groove‐binding tails that engage in noncovalent interactions with distant nucleotides, or that bind perpendicular to the DNA base pairs. Consequently, binding site models that include at least three adjacent nucleotides are required to consistently predict converged binding energies. The computationally inexpensive HF‐3c method is shown to provide reliable interaction energies and can be routinely applied to such large models.

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A DNA intercalation methodology for an efficient prediction of ligand binding pose and energetics

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 41 publications

References 68 publications

Challenges and current status of computational methods for docking small molecules to nucleic acids

Challenges and current status of computational methods for docking small molecules to nucleic acids

Flavonolignans from silymarin do not intercalate intoDNA: Rebuttal of data published in the paperJ. Mol. Recognit. e2812 (2019)

Importance of model size in quantum mechanical studies of DNA intercalation

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