Exploring the RNA-Recognition Mechanism Using Supervised Molecular Dynamics (SuMD) Simulations: Toward a Rational Design for Ribonucleic-Targeting Molecules?
Although proteins have represented the molecular target of choice in the development of new drug candidates, the pharmaceutical importance of ribonucleic acids has gradually been growing. The increasing availability of structural information has brought to light the existence of peculiar three-dimen...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2020.00107/full |
| _version_ | 1828789794434449408 |
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| author | Maicol Bissaro Mattia Sturlese Stefano Moro |
| author_facet | Maicol Bissaro Mattia Sturlese Stefano Moro |
| author_sort | Maicol Bissaro |
| collection | DOAJ |
| description | Although proteins have represented the molecular target of choice in the development of new drug candidates, the pharmaceutical importance of ribonucleic acids has gradually been growing. The increasing availability of structural information has brought to light the existence of peculiar three-dimensional RNA arrangements, which can, contrary to initial expectations, be recognized and selectively modulated through small chemical entities or peptides. The application of classical computational methodologies, such as molecular docking, for the rational development of RNA-binding candidates is, however, complicated by the peculiarities characterizing these macromolecules, such as the marked conformational flexibility, the singular charges distribution, and the relevant role of solvent molecules. In this work, we have thus validated and extended the applicability domain of SuMD, an all-atoms molecular dynamics protocol that allows to accelerate the sampling of molecular recognition events on a nanosecond timescale, to ribonucleotide targets of pharmaceutical interest. In particular, we have proven the methodological ability by reproducing the binding mode of viral or prokaryotic ribonucleic complexes, as well as that of artificially engineered aptamers, with an impressive degree of accuracy. |
| first_indexed | 2024-12-12T01:19:04Z |
| format | Article |
| id | doaj.art-b6faf05de35f453c914b68a66ecc858a |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-12T01:19:04Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-b6faf05de35f453c914b68a66ecc858a2022-12-22T00:43:17ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462020-02-01810.3389/fchem.2020.00107515945Exploring the RNA-Recognition Mechanism Using Supervised Molecular Dynamics (SuMD) Simulations: Toward a Rational Design for Ribonucleic-Targeting Molecules?Maicol BissaroMattia SturleseStefano MoroAlthough proteins have represented the molecular target of choice in the development of new drug candidates, the pharmaceutical importance of ribonucleic acids has gradually been growing. The increasing availability of structural information has brought to light the existence of peculiar three-dimensional RNA arrangements, which can, contrary to initial expectations, be recognized and selectively modulated through small chemical entities or peptides. The application of classical computational methodologies, such as molecular docking, for the rational development of RNA-binding candidates is, however, complicated by the peculiarities characterizing these macromolecules, such as the marked conformational flexibility, the singular charges distribution, and the relevant role of solvent molecules. In this work, we have thus validated and extended the applicability domain of SuMD, an all-atoms molecular dynamics protocol that allows to accelerate the sampling of molecular recognition events on a nanosecond timescale, to ribonucleotide targets of pharmaceutical interest. In particular, we have proven the methodological ability by reproducing the binding mode of viral or prokaryotic ribonucleic complexes, as well as that of artificially engineered aptamers, with an impressive degree of accuracy.https://www.frontiersin.org/article/10.3389/fchem.2020.00107/fullnucleic acidsRNASMIRNAmolecular recognitionmolecular dynamics (MD)supervised molecular dynamics (SuMD) |
| spellingShingle | Maicol Bissaro Mattia Sturlese Stefano Moro Exploring the RNA-Recognition Mechanism Using Supervised Molecular Dynamics (SuMD) Simulations: Toward a Rational Design for Ribonucleic-Targeting Molecules? Frontiers in Chemistry nucleic acids RNA SMIRNA molecular recognition molecular dynamics (MD) supervised molecular dynamics (SuMD) |
| title | Exploring the RNA-Recognition Mechanism Using Supervised Molecular Dynamics (SuMD) Simulations: Toward a Rational Design for Ribonucleic-Targeting Molecules? |
| title_full | Exploring the RNA-Recognition Mechanism Using Supervised Molecular Dynamics (SuMD) Simulations: Toward a Rational Design for Ribonucleic-Targeting Molecules? |
| title_fullStr | Exploring the RNA-Recognition Mechanism Using Supervised Molecular Dynamics (SuMD) Simulations: Toward a Rational Design for Ribonucleic-Targeting Molecules? |
| title_full_unstemmed | Exploring the RNA-Recognition Mechanism Using Supervised Molecular Dynamics (SuMD) Simulations: Toward a Rational Design for Ribonucleic-Targeting Molecules? |
| title_short | Exploring the RNA-Recognition Mechanism Using Supervised Molecular Dynamics (SuMD) Simulations: Toward a Rational Design for Ribonucleic-Targeting Molecules? |
| title_sort | exploring the rna recognition mechanism using supervised molecular dynamics sumd simulations toward a rational design for ribonucleic targeting molecules |
| topic | nucleic acids RNA SMIRNA molecular recognition molecular dynamics (MD) supervised molecular dynamics (SuMD) |
| url | https://www.frontiersin.org/article/10.3389/fchem.2020.00107/full |
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