Isoquinoline Alkaloids and Their Analogs: Nucleic Acid and Protein Binding Aspects, and Therapeutic Potential for Drug Design

2015 ◽  
pp. 241-278 ◽  
Author(s):  
Gopinatha S. Kumar
Keyword(s):  
Nucleic Acid ◽  
Drug Design ◽  
Protein Binding ◽  
Therapeutic Potential ◽  
Isoquinoline Alkaloids

scholarly journals Overlapping but distinct: a new model for G-quadruplex biochemical specificity

2021 ◽  
Author(s):  
Martin Volek ◽  
Sofia Kolesnikova ◽  
Katerina Svehlova ◽  
Pavel Srb ◽  
Ráchel Sgallová ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Drug Design ◽  
Solution Structure ◽  
Biochemical Data ◽  
Biological Regulation ◽  
New Model ◽  
G Quadruplex ◽  
Range Of Functions ◽  
Nucleic Acid Structures ◽  
Sequence Requirements

Abstract G-quadruplexes are noncanonical nucleic acid structures formed by stacked guanine tetrads. They are capable of a range of functions and thought to play widespread biological roles. This diversity raises an important question: what determines the biochemical specificity of G-quadruplex structures? The answer is particularly important from the perspective of biological regulation because genomes can contain hundreds of thousands of G-quadruplexes with a range of functions. Here we analyze the specificity of each sequence in a 496-member library of variants of a reference G-quadruplex with respect to five functions. Our analysis shows that the sequence requirements of G-quadruplexes with these functions are different from one another, with some mutations altering biochemical specificity by orders of magnitude. Mutations in tetrads have larger effects than mutations in loops, and changes in specificity are correlated with changes in multimeric state. To complement our biochemical data we determined the solution structure of a monomeric G-quadruplex from the library. The stacked and accessible tetrads rationalize why monomers tend to promote a model peroxidase reaction and generate fluorescence. Our experiments support a model in which the sequence requirements of G-quadruplexes with different functions are overlapping but distinct. This has implications for biological regulation, bioinformatics, and drug design.

scholarly journals Computer-Aided Drug Design (CADD) to De-Orphanize Marine Molecules: Finding Potential Therapeutic Agents for Neurodegenerative and Cardiovascular Diseases

Marine Drugs ◽  
2022 ◽  
Vol 20 (1) ◽  
pp. 53
Author(s):  
Laura Llorach-Pares ◽  
Alfons Nonell-Canals ◽  
Conxita Avila ◽  
Melchor Sanchez-Martinez
Keyword(s):  
Natural Products ◽  
Drug Design ◽  
Therapeutic Potential ◽  
Marine Invertebrate ◽  
In Silico Analysis ◽  
New Drugs ◽  
Computer Aided Drug Design ◽  
Marine Habitats ◽  
Computer Aided ◽  
Promising Line

Computer-aided drug design (CADD) techniques allow the identification of compounds capable of modulating protein functions in pathogenesis-related pathways, which is a promising line on drug discovery. Marine natural products (MNPs) are considered a rich source of bioactive compounds, as the oceans are home to much of the planet’s biodiversity. Biodiversity is directly related to chemodiversity, which can inspire new drug discoveries. Therefore, natural products (NPs) in general, and MNPs in particular, have been used for decades as a source of inspiration for the design of new drugs. However, NPs present both opportunities and challenges. These difficulties can be technical, such as the need to dive or trawl to collect the organisms possessing the compounds, or biological, due to their particular marine habitats and the fact that they can be uncultivable in the laboratory. For all these difficulties, the contributions of CADD can play a very relevant role in simplifying their study, since, for example, no biological sample is needed to carry out an in-silico analysis. Therefore, the amount of natural product that needs to be used in the entire preclinical and clinical study is significantly reduced. Here, we exemplify how this combination between CADD and MNPs can help unlock their therapeutic potential. In this study, using a set of marine invertebrate molecules, we elucidate their possible molecular targets and associated therapeutic potential, establishing a pipeline that can be replicated in future studies.

Role of Molecular Docking in Computer-Aided Drug Design and Development

2016 ◽  
pp. 1-28
Author(s):  
Rahul Agarwal ◽  
Ashutosh Singh ◽  
Subhabrata Sen
Keyword(s):  
Molecular Docking ◽  
Drug Design ◽  
Protein Binding ◽  
Design And Development ◽  
Advantages And Disadvantages ◽  
Computer Aided ◽  
Drug Designing ◽  
Near Future

Molecular Docking is widely used in CADD (Computer-Aided Drug Designing), SBDD (Structure-Based Drug Designing) and LBDD (Ligand-Based Drug Designing). It is a method used to predict the binding orientation of one molecule with the other and used for any kind of molecule based on the interaction like, small drug molecule with its protein target, protein – protein binding or a DNA – protein binding. Docking is very much popular technique due to its reliable prediction properties. This book chapter will provide an overview of diverse docking methodologies present that are used in drug design and development. There will be discussion on several case studies, pertaining to each method, followed by advantages and disadvantages of the discussed methodology. It will typically aim professionals in the field of cheminformatics and bioinformatics, both in academia and in industry and aspiring scientists and students who want to take up this as a profession in the near future. We will conclude with our opinion on the effectiveness of this technology in the future of pharmaceutical industry.

Nucleic acid targeted drug design

1993 ◽  
Vol 14 (10) ◽  
pp. 385-386
Author(s):  
James M. Veal
Keyword(s):  
Nucleic Acid ◽  
Drug Design ◽  
Targeted Drug

scholarly journals How ‘Protein-Docking’ Translates into the New Emerging Field of Docking Small Molecules to Nucleic Acids?

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2749
Author(s):  
Francesca Tessaro ◽  
Leonardo Scapozza
Keyword(s):  
Molecular Docking ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Small Molecules ◽  
Viral Infections ◽  
Therapeutic Potential ◽  
Mrna Level ◽  
Protein Docking ◽  
Structural Nature ◽  
Rigid Docking

In this review, we retraced the ‘40-year evolution’ of molecular docking algorithms. Over the course of the years, their development allowed to progress from the so-called ‘rigid-docking’ searching methods to the more sophisticated ‘semi-flexible’ and ‘flexible docking’ algorithms. Together with the advancement of computing architecture and power, molecular docking’s applications also exponentially increased, from a single-ligand binding calculation to large screening and polypharmacology profiles. Recently targeting nucleic acids with small molecules has emerged as a valuable therapeutic strategy especially for cancer treatment, along with bacterial and viral infections. For example, therapeutic intervention at the mRNA level allows to overcome the problematic of undruggable proteins without modifying the genome. Despite the promising therapeutic potential of nucleic acids, molecular docking programs have been optimized mostly for proteins. Here, we have analyzed literature data on nucleic acid to benchmark some of the widely used docking programs. Finally, the comparison between proteins and nucleic acid targets docking highlighted similarity and differences, which are intrinsically related to their chemical and structural nature.

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