Pharmacobiomatics
From Biomatics.org
Pharmacology (from Greek φάρμακον, pharmakon, "drug"; and -λογία, -logia) is the study of drug action.[1] More specifically it is the study of the interactions that occur between a living organism and exogenous chemicals that alter normal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals. The field encompasses drug composition and properties, interactions, toxicology, therapy, and medical applications and antipathogenic capabilities. Pharmacology is not synonymous with pharmacy, which is the name used for a profession, though in common usage the two terms are confused at times. Pharmacology deals with how drugs interact within biological systems to affect function. It is the study of drugs, of the body's reaction to drugs, the sources of drugs, their nature, and their properties. In contrast, pharmacy is a medical science concerned with the safe and effective use of medicines.
The origins of clinical pharmacology date back to the Middle Ages in Avicenna's The Canon of Medicine, Peter of Spain's Commentary on Isaac, and John of St Amand's Commentary on the Antedotary of Nicholas.[2] Pharmacology as a scientific discipline did not further advance until the mid-19th century amid the great biomedical resurgence of that period.[3] Before the second half of the nineteenth century, the remarkable potency and specificity of the actions of drugs such as morphine, quinine and digitalis were explained vaguely and with reference to extraordinary chemical powers and affinities to certain organs or tissues.[4] The first pharmacology department was set up by Buchheim in 1847, in recognition of the need to understand how therapeutic drugs and poisons produced their effects.[3]
Early pharmacologists focused on natural substances, mainly plant extracts. Pharmacology developed in the 19th century as a biomedical science that applied the principles of scientific experimentation to therapeutic contexts.[5]
Pharmacokinetics (in Greek: “pharmacon” meaning drug and “kinetikos” meaning putting in motion, the study of time dependency; sometimes abbreviated as “PK”) is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism. In practice, this discipline is applied mainly to drug substances, though in principle it concerns itself with all manner of compounds ingested or otherwise delivered externally to an organism, such as nutrients, metabolites, hormones, toxins, etc.
Pharmacokinetics is often studied in conjunction with pharmacodynamics. Pharmacodynamics explores what a drug does to the body, whereas pharmacokinetics explores what the body does to the drug. Pharmacokinetics includes the study of the mechanisms of absorption and distribution of an administered drug, the rate at which a drug action begins and the duration of the effect, the chemical changes of the substance in the body (e.g. by enzymes) and the effects and routes of excretion of the metabolites of the drug.[1]
Pharmacogenomics is the branch of pharmacology which deals with the influence of genetic variation on drug response in patients by correlating gene expression or single-nucleotide polymorphisms with a drug's efficacy or toxicity. By doing so, pharmacogenomics aims to develop rational means to optimise drug therapy, with respect to the patients' genotype, to ensure maximum efficacy with minimal adverse effects. Such approaches promise the advent of "personalized medicine"; in which drugs and drug combinations are optimized for each individual's unique genetic makeup.[1]
Pharmacogenomics is the whole genome application of pharmacogenetics, which examines the single gene interactions with drugs.
Pharmacognosy is the study of medicines derived from natural sources. The American Society of Pharmacognosy[1] defines pharmacognosy as "the study of the physical, chemical, biochemical and biological properties of drugs, drug substances or potential drugs or drug substances of natural origin as well as the search for new drugs from natural sources."
Pharmacobiomatics
Pharmacobiomatics is: Characterizing the interaction of drugs with biomachines (proteins, protein networks, reaction networks, protein automata etc) at the molecular, sub cellular, cellular, tissue, organ, individual, and populational levels.
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Posttranslational modification
Posttranslational modification (PTM) is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis for many proteins.
A protein (also called a polypeptide) is a chain of amino acids. During protein synthesis, 20 different amino acids can be incorporated in proteins. After translation, the posttranslational modification of amino acids extends the range of functions of the protein by attaching to it other biochemical functional groups such as acetate, phosphate, various lipids and carbohydrates, by changing the chemical nature of an amino acid (e.g. citrullination) or by making structural changes, like the formation of disulfide bridges.
Also, enzymes may remove amino acids from the amino end of the protein, or cut the peptide chain in the middle. For instance, the peptide hormone insulin is cut twice after disulfide bonds are formed, and a propeptide is removed from the middle of the chain; the resulting protein consists of two polypeptide chains connected by disulfide bonds. Also, most nascent polypeptides start with the amino acid methionine because the "start" codon on mRNA also codes for this amino acid. This amino acid is usually taken off during post-translational modification.
Other modifications, like phosphorylation, are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme.
Signaling protein networks as targets of new antineoplastic drugs.
Laboratory of Experimental Oncology, Department of Cell Biology and Oncology, Mario Negri Institute-Consorzio Mario Negri Sud, Santa Maria Imbaro (CH), Italy. alberti@negrisud.it
In-depth analysis of molecular regulatory networks in cancer holds the promise of improved knowledge of the pathophysiology of tumor cells so that it will become possible to design a detailed molecular tumor taxonomy. This knowledge will also offer new opportunities for the identification and validation of key molecular tumor targets to be exploited for novel therapeutic approaches. Some signaling proteins have already been identified as such, e.g. c-Myc, Cyclin D1, Bcl-XL, kinases and some nuclear receptors. This has led to the successful development of a few function-modulatory drugs (Glivec, SERM, Iressa), providing proof-of-principle of the validity of this approach. Further developments are likely to derive from "-omic" approaches, aimed at the understanding of signaling networks and of the mechanism of action of newfound lead molecules. High-throughput screening of small drug-like molecules from combinatorial chemical libraries or from microbial extracts will identify novel, "intelligent" drug candidates. An additional medicinal chemistry strategy (via 40-50 unit rosary-bead chains) has the potential to be much more effective than small molecules in interfering with protein-protein interactions. This may lead to considerably higher selectivity and effectiveness compared with historical approaches in drug discovery.
Bio-molecular structure and intermolecular interactions
We look into structure-function relations of proteins; protein-peptides and protein-lipid complexes (Fig 1) forming unique nanostructures. We are studying how the presence or absence of chemical energy affects the structure and interactions of the complexes.
Fig 1. "Smart bionanotubes" - with open or closed ends - that could be developed for drug or gene delivery applications. By manipulating the electrical charges of lipid bilayer membranes and microtubules (proteins from cell cytoskeleton) and the protein/lipid molar ration, we could create open (right) or closed (left) bio-nanotubes, or nanoscale capsules. The image shows a schematic of the lipid protein nanotubes made of microtuble protein (made of tubulin protein subunits shown as red-blue-yellow-green objects) that is coated by a lipid bilayer (drawn with yellow tails and green and white spherical heads) which in turn is coated by tubulin protein rings or spirals. By controlling the relative amount of charged and neutral lipids it is also possible to control the size of the inner nanotube. Based on Figure 1 and cover of Raviv, et al. Biophys. J. 92 (1), 278-287 (2007).
Drugs and Protein Folding
What is protein folding and how is folding linked to disease? Proteins are biology's workhorses -- its "nanomachines." Before proteins can carry out these important functions, they assemble themselves, or "fold." The process of protein folding, while critical and fundamental to virtually all of biology, in many ways remains a mystery. Moreover, when proteins do not fold correctly (i.e. "misfold"), there can be serious consequences, including many well known diseases, such as Alzheimer's, Mad Cow (BSE), CJD, ALS, Huntington's, Parkinson's disease, and many Cancers and cancer-related syndromes.
Diseases (41)
Simulations (17)
Stability (15)
Binding (14)
Chemical (17)
Protein Folding Problem (13)
Protein Structure (11)
Chaperones (9)
Game, Researchers Launch (8)
Distributed, Computing (6)
External Links
Pharmaceutical Proteomics Glossary & Taxonomy
