Nucleic Acid Quadratic Indices of the “Macromolecular Graph's Nucleotides Adjacency Matrix”. Modeling of Footprints after the Interaction of Paromomycin with the Hiv-1 Ψ-Rna Packaging Region

Science Direct Working Paper No S1574-0331(04)70146-0

24 Pages Posted: 14 Jun 2017 Last revised: 6 Jan 2018

See all articles by Yovani Ponce

Yovani Ponce

Central University of Las Villas - Department of Pharmacy

Delvin Nodarse

Central University of Las Villas - Department of Pharmacy

Humberto Díaz

Universidade de Santiago de Compostela - Department of Organic Chemistry

Ronal de Armas

Central University of Las Villas - Department of Drug Design

Vicente Zaldivar

University of Cienfuegos - Faculty of Informatics

Francisco Torrens

University of Valencia - Institut Universitari de Ciència Molecular

Eduardo Alberto Castro

Universidad Nacional de La Plata - Departamento de Quimica

Date Written: January 2004

Abstract

This report describes a new set of macromolecular descriptors of relevance to nucleic acid QSAR/QSPR studies, nucleic acid’s quadratic indices. These descriptors are calculated from the macromolecular graph’s nucleotides adjacency matrix. A study of the interaction of the antibiotic Paromomycin with the packaging region of the RNA present in type-1 HIV illustrates this approach. A linear discriminant function gave rise to excellent discrimination between 90.10% (91/101) and 81.82% (9/11) of interacting/noninteracting sites of nucleotides in training and test set, respectively. The LOO cross-validation procedure was used to assess the stability and predictability of the model. Using this approach, the classification model has shown a LOO global good classification of 91.09%. In addition, the model’s overall predictability oscillates from 89.11% until 87.13%, when varies from 2 to 3 in leave--out jackknife method. This value stabilizes around 88.12% when was > 3. On the other hand, a linear regression model predicted the local binding affinity constants [log (10M)] between a specific nucleotide and the aforementioned antibiotic. The linear model explains almost 92% of the variance of the experimental log (R = 0.96 and s = 0.07) and LOO press statistics evidenced its predictive ability ( = 0.85 and s = 0.09). These models also permit the interpretation of the driving forces of the interaction process. In this sense, developed equations involve short-reaching ( ≤ 3), middle-reaching (4 < < 9) and far-reaching ( = 10 or greater) nucleotide’s quadratic indices. This situation points to electronic and topologic nucleotide’s backbone interactions control of the stability profile of Paromomycin-RNA complexes. Consequently, the present approach represents a novel and rather promising way to chem & bioinformatics research.

Keywords: Footprinting, Paromomycin, RNA VIH-1, TOMOCOMD approach, Nucleic Acid Quadratic Index, QSPR

Suggested Citation

Ponce, Yovani and Nodarse, Delvin and Díaz, Humberto and de Armas, Ronal and Zaldivar, Vicente and Torrens, Francisco and Castro, Eduardo Alberto, Nucleic Acid Quadratic Indices of the “Macromolecular Graph's Nucleotides Adjacency Matrix”. Modeling of Footprints after the Interaction of Paromomycin with the Hiv-1 Ψ-Rna Packaging Region (January 2004). Science Direct Working Paper No S1574-0331(04)70146-0, Available at SSRN: https://ssrn.com/abstract=2978949

Yovani Ponce (Contact Author)

Central University of Las Villas - Department of Pharmacy ( email )

Villa Clara, 54830
Cuba

Delvin Nodarse

Central University of Las Villas - Department of Pharmacy

Villa Clara, 54830
Cuba

Humberto Díaz

Universidade de Santiago de Compostela - Department of Organic Chemistry

15706
Spain

Ronal De Armas

Central University of Las Villas - Department of Drug Design

Villa Clara, 54830
Cuba

Vicente Zaldivar

University of Cienfuegos - Faculty of Informatics

Cienfuegos
Cuba

Francisco Torrens

University of Valencia - Institut Universitari de Ciència Molecular

Dr. Moliner 50
València, E-46100
Spain

Eduardo Alberto Castro

Universidad Nacional de La Plata - Departamento de Quimica ( email )

Calle 47 y 115
La Plata, 1900
Argentina

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