RESUMO
Molecular modeling by means of docking and molecular dynamics (MD) has become an integral part of early drug discovery projects, enabling the screening and enrichment of large libraries of small molecules. In the past decades, special emphasis was drawn to nucleic acid (NA)-based molecules in the fields of therapy, diagnosis, and drug delivery. Research has increased dramatically with the advent of the SELEX (systematic evolution of ligands by exponential enrichment) technique, which results in single-stranded DNA or RNA sequences that bind with high affinity and specificity to their targets. Herein, we discuss the role and contribution of docking and MD to the development and optimization of new nucleic acid-based molecules. This review focuses on the different approaches currently available for molecular modeling applied to NA interaction with proteins. We discuss topics ranging from structure prediction to docking and MD, highlighting their main advantages and limitations and the influence of flexibility on their calculations.
Assuntos
DNA/química , Descoberta de Drogas/métodos , Modelos Moleculares , RNA/química , Animais , DNA/metabolismo , Humanos , RNA/metabolismoRESUMO
Apicomplexan parasites cause infectious diseases that are either a severe public health problem or an economic burden. In this paper we will shed light on how oxidative stress can influence the host-pathogen relationship by focusing on three major diseases: babesiosis, coccidiosis, and toxoplasmosis.
Assuntos
Babesia/metabolismo , Cryptosporidium/metabolismo , Estresse Oxidativo , Toxoplasma/metabolismo , Animais , Babesia/patogenicidade , Babesiose/metabolismo , Babesiose/parasitologia , Babesiose/patologia , Coccidiose/metabolismo , Coccidiose/parasitologia , Coccidiose/patologia , Cryptosporidium/patogenicidade , Interações Hospedeiro-Parasita , Humanos , Toxoplasma/patogenicidade , Toxoplasmose/metabolismo , Toxoplasmose/parasitologia , Toxoplasmose/patologiaRESUMO
Malaria is a deadly infectious disease which affects millions of people each year in tropical regions. There is no effective vaccine available and the treatment is based on drugs which are currently facing an emergence of drug resistance and in this sense the search for new drug targets is indispensable. It is well established that vitamin biosynthetic pathways, such as the vitamin B6 de novo synthesis present in Plasmodium, are excellent drug targets. The active form of vitamin B6, pyridoxal 5-phosphate, is, besides its antioxidative properties, a cofactor for a variety of essential enzymes present in the malaria parasite which includes the ornithine decarboxylase (ODC, synthesis of polyamines), the aspartate aminotransferase (AspAT, involved in the protein biosynthesis), and the serine hydroxymethyltransferase (SHMT, a key enzyme within the folate metabolism).
Assuntos
Aspartato Aminotransferases/metabolismo , Glicina Hidroximetiltransferase/metabolismo , Malária/enzimologia , Ornitina Descarboxilase/metabolismo , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/genética , Glicina Hidroximetiltransferase/genética , Humanos , Malária/genética , Malária/parasitologia , Ornitina Descarboxilase/genética , Plasmodium falciparum/enzimologia , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidade , Vitamina B 6/metabolismoRESUMO
Worldwide the entire human population is at risk of infectious diseases of which a high degree is caused by pathogenic protozoans, worms, bacteria, and virus infections. Moreover the current medications against pathogenic agents are losing their efficacy due to increasing and even further spreading drug resistance. Therefore, there is an urgent need to discover novel diagnostic as well as therapeutic tools against infectious agents. In view of that, the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) represents a powerful technology to target selectively pathogenic factors as well as entire bacteria or viruses. SELEX uses a large combinatorial oligonucleic acid library (DNA or RNA) which is processed a by high-flux in vitro screen of iterative cycles. The selected ligands, termed aptamers, are characterized by high specificity and affinity to their target molecule, which are already exploited in diagnostic and therapeutic applications. In this minireview we will discuss the current status of the SELEX technique applied on bacterial and viral pathogens.