Amongst the latest buzzwords tailor-made to fox the previous generation whilst gladdening the hearts of todays scientists, is bio-informatics: however this term implys the wedding of biology and information technology, informatics itself being a blurry concept for most of us to begin with. Here are a few definitions.
What is Bio-informatics?
Bio-informatics is the application of computer technology to the management of biological information. Computers are used to gather, store, analyse and integrate biological and genetic information, which can then be applied to gene-based drug discovery and development. The explosion of publicly available genomic information resulting from the Human Genome Project has precipitated the need for Bio-informatics capabilities. The goal of this project - determination of the sequence of the entire human genome (approximately three billion base pairs) - was to be reached by the year 2002.
The science of Bioinformatics, which is the melding of molecular biology with computer science, is essential to the use of genomic information in understanding human diseases and in the identification of new molecular targets for drug discovery. In recognition of this, many universities, government institutions and pharmaceutical firms have formed bioinformatics groups, consisting of computational biologists and bioinformatics computer scientists. Such groups will be key to sort out the mass of information generated by large scale sequencing efforts underway in laboratories around the world.
What is Bioinformatics? - The Tight Definition
Most biologists talk about "doing bioinformatics" when they use computers to store, retrieve, analyse or predict the composition or the structure of biomolecules. As computers become more powerful you could probably add simulate to this list of bioinformatics verbs. "Biomolecules" include your genetic material nucleic acids and the products of your genes: proteins. Fredj Tekaia at the Institute Pasteur offers this definition of bioinformatics: "The mathematical, statistical and computing methods that aim to solve biological problems using DNA and amino acid sequences and related information."
It is a mathematically interesting property of most large biological molecules that they are polymers; ordered chains of simpler molecular modules called monomers. Think of the monomers as beads or building blocks, which, despite having different colours and shapes, all have the same thickness and the same way of connecting to one another. Monomers that can combine in a in a chain are of the same general class, but each kind of monomer in that class has its own well-defined set of characteristics. Many monomer molecules can be joined together to forma single, far larger, macromolecule. The macromolecule can have exquisitely specific informational content and/or chemical properties.
"New bio-informatics"
The greatest achievement of bioinformatics methods, the Human Genome Project. Because of this the nature and priorities of bioinformatics research and applications are changing. Many experts believe that this will affect bioinformatics in several ways. For instance some scientists also believe what some people refer to as research or medical informatics, the management of all biomedical experimental data associated with particular molecules or patients - from mass spectroscopy, to in vitro assays to clinical side-effects-move from the concern of those working in drug company and hospital IT (information technology) into the mainstream of cell and molecular biology and migrate from the commercial and clinical to academic sectors.
Drug Development
Only 10% of drug molecules identified in research make it through development. This means that many potential drugs do not make it to market, and expensive time and resources are invested m molecules that will generate no revenue. Simulation and informatics can significantly increase these odds by improving the efficiency of drug development, cutting costs, and improving margins.
Formulation Design
Formulation is the process of mixing Ingredients in such a way as to produce a new or improved product. The formulation department must balance the different marketing and deliverability requirements with cost and chemical constraints to come up with the best possible drug delivery method at the best price. With laboratory results stored in legacy systems, it takes expert company knowledge and experience to know which methods and suppliers are available, let alone to locate them quickly. In many cases scientists find that it is easier to repeat an experiment than to find previous results. This situation is compounded in global R&D set-ups, and after mergers and acquisitions.
With an aging workforce, management watches skills and knowledge leave the company, with the replacement prospects at best being expensive; at worst non-existent. Knowledge management offers solutions to these problems. Storing information in a corporate database means that scientists can access results and methods from anywhere in the world. They can use their time and resources on new research, rather than repeating old work. Using computer technology to manage an organisations knowledge also helps to plan for and minimize the erosion of skills, ensuring that projects run smoothly and efficiently.
Crystallisation and Structure Determination
Determining the crystal structure of an active compound is one of the first steps in pharmaceutical development. The crystal structure of a drug affects how easy it is to formulate, its bio-avail- ability, and its shelf life. Knowledge of the different possible polymorphs of a crystal can also give better patent protection for a drug.
Crystal structure is generally solved by diffraction. Single X-ray diffraction is a reliable method of structure determination, but requires the often difficult and time-consuming growth of a large and pure crystal of the material. Powder X-ray diffraction produces a spectrum from the ground up crystalline material, making it easier to produce experimentally, but harder to determine the crystal structure from the resulting powder diffraction pattern. Readymade software such as Accelrys Reflex Plus provides a comprehensive solution for crystal structure solution.
Once a drug has been crystallised, it is usually the crystal form that is patented. Should a competitor find another polymorph of the drug, it may be possible for them to patent and market the new polymorph. Companies also run the danger of an unwanted polymorph being produced unexpectedly in manufacturing. It is very difficult to determine all possible polymorphs by experimentation, since different conditions may produce different polymorphs.
Polymer Modeling
Drug delivery is a complex task. The drug must be delivered in a way that transports the active component intact to the appropriate part of the body. The way the cell takes up the drug is also very important: drugs that go to parts of the body other than the intended target are wasted and may lead to unwanted side effects.
Many delivery devices are polymeric with the drug either solubilised or emulsified in the polymer. Drug delivery systems have mesoscale structures; between 10 to 1000 nm. The amount of computing power required to model these systems at an atomistic level is prohibitive, and macroscale techniques such as Finite element analysis or computational fluid dynamics do not give the required level of detail. Mesoscale modeling, focusing on the nanometer length scale, is helping scientists to develop colloidal delivery systems for drugs.
Only 10% of drug molecules identified in research make it through development. This means that many potential drugs do not make it to market, and expensive time and resources are invested in molecules that will generate no revenue. Simulation and informatics ca significantly increase these odds by improving the efficiency of drug development, cutting costs, and improving margins.
Achieving a suitable formulation d the drug candidate can determine the rat at which a drug gains FDA approval Detailed knowledge of the crystal structure of the drug affects the level of paten control. Techniques such as polymer modelling are helping to create new methods of drug delivery.
With the announcement of the sue successful experiments in making tiny biomolecules which are in reality computer chip like and thus can anticipate the formation of diseased cells and signal the defense mechanism of the body to start manufacturing antibodies, drug delivery and health management will take up new meanings perhaps.
