References

The efficiency of multi-target drugs the network approach might help drug design. Trends Pharmacol Sci 2005 26 178-82. 2. Walgren JL, Thompson DC. Application of proteomic technologies in the drug development process. Toxicol Lett 2004 149 377-85. 3. Hood L, Heath JR, Phelps ME, Lin B. Systems biology and new technologies enable predictive and preventative medicine. Science 2004 306 640-3. 4. Westerhoff HV, Palsson BO. The evolution of molecular biology into...

Growth The 1980s

If the 1960s were the Dark Ages and the 1970s were the Middle Ages, the 1980s were the Renaissance, the Baroque Period, and the Enlightenment all rolled into one. The decade of the 1980s was when the various approaches of quantum chemistry, molecular mechanics, molecular simulations, QSAR, and molecular graphics coalesced into modern computational chemistry. In the world of scientific publishing, a seminal event occurred in 1980. Professor Allinger launched his Journal of Computational...

Beyond the Ultra Link

The purpose of the UltraLink is not only to comfortably navigate across distributed knowledge sources but also to access a variety of analysis tools. In this section, we illustrate this functionality through a few of the implemented tools, building on the previous psoriasis example. Let's follow the UltraLink provided for psoriasis in Figure 31.2C psoriasis disease Portfolio Analysis It links to a proprietary strategic analysis platform that uses the normalized term for performing a portfolio...

Electronic Registration Systems for the Medicinal Chemist

As one of the indispensable software tools, the compound registration system provides a mechanism for the medicinal chemist to capture chemical structure information as well as analytical and other data in a database. We mention two of the systems below. CambridgeSoft's registration system keeps track of newly synthesized or acquired compounds and their physical properties and assigns unique compound identifiers. This system is a Web-based application for storing and searching over a...

Active Transport

Transporters should be an integral part of any ADMET modeling program because of their ubiquitous presence on barrier membranes and the substantial overlap between their substrates and many drugs. Unfortunately, because of our limited understanding of transporters, most prediction programs do not have a mechanism to incorporate the effect of active transport. However, interest in these transporters has resulted in a relatively large amount of in vitro data, which in turn have enabled the...

The Web Interface

In Section 31.4, we explained the data structure that we use to represent and build an UltraLink. Now, we outline how the Web interface of the KSP assembles the information to user-friendly dialogs. Figure 31.2A shows the results of a simple query sent to the KSP (list of ranked documents records) and how the extracted concepts are displayed. The concepts are grouped into color-coded types (Figure 31.2B, keywords). The recognized entities are presented as a set of clickable concepts highlighted...

Power And Predictive Biosimulation 3241 Petaflop and Grid Computing

The simulation of events as complicated as the interaction of biological systems such as protein folding, cells, organs, and whole organisms requires both elegant algorithms and enormous computer power 9 . This chapter will not describe the intricacies of grid and supercomputing except to say that a new generation of petaflop computers will enable Pharma to begin large-scale biomolecular simulations. To give an example, the computational effort required to study protein folding is enormous....

Data Utilization Extraction And Standards

Currently the NIH road map is driving a systems biology agenda, with academia and government trying to facilitate this. Systems biology at the moment is significantly dominated by genomic experimental data and networks, and it is perhaps telling that the NIH and FDA have access to virtually all commercially available network-building software and databases. The FDA has released a guidance for industry on the use of pharmacogenomics data for drug safety evaluation and is actively working to...

Germination The 1960s

We can state confidently that in 1960 essentially 100 of the computational chemists were in academia, not industry. Of course, back then they were not called computational chemists, a term not yet invented. They were called theoretical chemists or quantum chemists. The students coming from those academic laboratories constituted the main pool of candidates that industry could hire for their initial ventures into using computers for drug discovery. Another pool of chemists educated using...

Statistical Pharmacophore And Homology Models And Crystal Structures Of Drugmetabolizing Enzymes

In the 1960s it was discovered that a mathematical model could describe the relationship between simple calculated molecular properties for a series of TABLE 18.1 Human Enzymes Involved in Drug Metabolism That Have Been Computationally Modeled to Date TABLE 18.1 Human Enzymes Involved in Drug Metabolism That Have Been Computationally Modeled to Date Abbreviations NADPH, b-nicotinamide adenine dinucleotide phosphate reduced from FAD, flavin adenine dinucleotide PAPS, 3'-phosphoadenosine...

Cheminformatics and Compound Library Design

Because of space limitations, we cannot cover extensively the applications of the aforementioned tools in both lead generation and lead optimization programs. However, it is worth saying a few words about their applications in the design of chemical libraries for biological screening purposes. The cheminformatics technologies, including similarity diversity assessment, pharmacophore modeling, the QSAR technique, ADMET Tox modeling, as well as the structure-based docking tools, have all found...

Risk Infection Care Plan

Eisenberg JM, Freund D, Glick H, et al. Clinical economics education in the International Clinical Epidemiology Network. INCLEN Economics Faculty. J Clin Epidemiol 1989 42 689-95. 2. Weinstein MC, Stason WB. Foundations of cost-effectiveness analysis for health and medical practices. N Engl J Med 1977 296 716-21. 3. Pare D, Freed M. Clinical practice guidelines for quality patient outcomes. Nurs Clin North Am 1995 30 183-96. 4. Winslow R. Study compares role of doctors in cardiac cases. Wall...

Introduction

Anyone who has worked for some time in the pharmaceutical industry has a story of how a successful drug was developed after a fortuitous coffee machine encounter between two or more scientists, or how a problem was not discovered until late-stage development because an important piece of information was missed. A tragic example described in the literature tells of a 24-year-old woman who died in 2001 after participating in a research study involving administration of hexamethonium bromide by...

Systems Biology Commercial Applications

A recent review has described the numerous commercial concerns that are involved in systems biology by providing either software or services 24 . Large, curated interaction databases combined with powerful analytical and network building tools are commercially available from companies like GeneGo Inc. MetaCore , Ariadne Genomics Inc. Pathway Studio , Ingenuity Inc. Pathways Analysis , and Jubilant Biosys PathArt that cover human metabolism, regulation, and signaling Table 6.1 . Currently there...

Bioinformatics And Vaccine Discovery

Immunoinformatics is a newly emergent subdiscipline within the informatic sciences that deals specifically with the unique problems of the immune system. Like bioinformatics, immunoinformatics complements, but never replaces, laboratory experimentation. It allows researchers to address, in a systematic manner, the most important questions in the still highly empirical world of immunology and vaccine discovery. The first vaccine was discovered by Edward Jenner in 1796, when he used cowpox, a...

Protein Coupled Receptors GPCRs

A model of the a1A adrenergic receptor was generated by ligand-supported homology modeling, based on the highresolution X-ray structure of bovine rhodopsin and also using mutational and ligand SAR data. Virtual screening of the Aventis in-house compound repository was then performed in a stepwise manner. First, compounds with more than nine rotatable bonds and molecular weight gt 600 were eliminated then 22,950 compounds were selected, using a a1A receptor ligand...

Computers As Data Analysis And Data Management Tools In Preclinical Development

2.2 Chromatographic Data Systems CDS 2.2.2 The Emergence and Evolution of CDS 2.3 Laboratory Information Management Systems LIMS 2.3.1 LIMS Hardware and Architectures 2.4 Text Information Management Systems TIMS 2.4.1 Documentation Requirements in Preclinical Development Computer Applications in Pharmaceutical Research and Development, Edited by Sean Ekins. ISBN 0-471-73779-8 Copyright 2006 John Wiley amp Sons, Inc. Scientists from many different disciplines participate in pharmaceutical...

Fruition The 1990s

The 1990s was a decade of fruition because the computer-based drug discovery work of the 1980s yielded an impressive number of new chemical entities reaching the pharmaceutical marketplace. We elaborate on this statement later in this section, but first we complete the story about supercomputers in the pharmaceutical industry. Pharmaceutical companies were accustomed to supporting their own research and making large investments in it. In fact, the pharmaceutical industry has long maintained the...

Contributors

Mazen Abdellatif, Hines VA Cooperative Studies Program Coordinating Center 151K , P.O. Box 5000, 5th Ave. and Roosevelt Rd. Bldg. 1, Rm. B240, Hines, IL 60141-5000, USA. mazen.abdellatif med.va.gov . Heather Ahlborn, IBM Business Consulting Services, Pharma and Life Sciences, Armonk, NY 10504, USA. ahlborn us.ibm.com . Konstantin V. Balakin, ChemDiv, Inc. 11558 Sorrento Valley Rd., Ste. 5, San Diego, CA 92121, USA. kvb chemdiv.com . Kenneth Banks, Global Analytical Development, Johnson amp...