数据库

This chapter provides a bottom-up perspective on bioinformatics data standards, beginning with a historical perspective on biochemical nomenclature standards. Various file format standards were soon developed to convey increasingly complex and voluminous data that nome ...

Mutation and selection are the principle forces governing gene and protein sequence. Mutation is the major source of variation, and selection removes variation. Although many mutations are likely to be neutral with respect to natural selection, much of the extant sequence that is functio ...

Elucidation of the entire human genomic sequence is one of the greatest achievements of science. Understanding the functional role of 30,000 human genes and more than 2 million polymorphisms was possible through a multidisciplinary approach using microarrays and bioinformatics. ...

Understanding the interactions of proteins with other proteins and/or with drug molecules is essential for understanding the progression of diseases. In this chapter, we present several methods utilizing mass spectrometry (MS) for the analysis of protein-protein, protein-drug, ...

In the late 1970s and early 1980s, the components that have made modern high-throughput screening (HTS) laboratory possible came together. Those were: 1) small scale servo-driven robotic devices; 2) the personal computer; and 3) the microplate. The word “robot” is derived from the Czechoslov ...

This chapter will explain the unit automation approach to high throughput screening. The unit automation approach is predicated on the belief that automation is best implemented only to the extent that operations are standardized, i.e., if you standardize individual assay steps (or unit ...

The object of all high throughput screening (HTS) laboratories is to provide the pharmaceutical research community with potentially active compounds rapidly and in the most cost effective manner possible. The most reliable way this can be achieved is by rigorous attention to the quality of ...

As a scientist or manager involved with high throughput screening (HTS), you have a wide range of options when selecting the degree of automation to support your discovery efforts. You will want to think about your anticipated needs 2–4 yr (or more) into the future and whether those projected needs wi ...

Rapid progress in the fields of genomics, proteomics, and molecular biology has both increased the numbers of potential drug targets, and facilitated development of assays to screen these targets (1–5). In parallel with these changes, developments in robotics and combinatorial chemi ...

In most pharmaceutical and biotechnology companies, high throughput screening (HTS) is a central function in the drug-discovery process. This has resulted from the fact that there are increasing numbers of validated therapeutic targets being discovered through advances in human g ...

Radioligand binding is a well-established technique that has been used to study the interactions of extracellular ligands and their corresponding cell-surface receptors (1). The initial studies relied on laborious, vacuum-filtration techniques that are cumbersome and diffi ...

During the last few years, a variety of technologies have been developed for rapid discovery of protein kinase inhibitors from both synthetic small-molecule libraries and natural products (1–8). Many of high throughput kinase assays have been developed in 96-, 384-, and 1536-well formats us ...

Biochemical assays used in high-throughput screening (HTS) to identify lead compounds in drug discovery have been formatted using a wide variety of detection techniques. These include radiometric, colorimetric, fluorescent, and enzyme-linked immunosorbent assays (ELISA). ...

Cell-based screens represent one of the most venerable approaches to lead generation, indeed, antimicrobial screens were the mainstay of drug discovery in the 1940s, 1950s, and 1960s (1). However, cellular assays also represent one of the most dynamic areas of innovation in high-throughp ...

The growing number of compounds synthesized and screened in the phar-maceutical industry due to the rapid development of high-throughput chemis-try and screening technologies are a response to the need of more and better quality compounds in the industry pipelines. But these inmense co ...

The Automated Liquid Sample Bank (ALSB) is a key component of our strategy to increase drug-discovery productivity and to reduce manning requirements wherever possible.

Natural products are undeniably the best source for diversity in chemotype for the discovery of novel therapeutics. One-third of the top selling drugs in the world are natural products or their derivatives (Fig. 1). Roughly 60% of the antitumor and anti-infective agents that are available com ...

Molecular simulation is a very powerful toolbox in modern molecular modeling, and enables us to follow and understand structure and dynamics with extreme detail—literally on scales where motion of individual atoms can be tracked. This chapter focuses on the two most commonly used methods, ...

A description of Monte Carlo methods for simulation of proteins is given. Advantages and disadvantages of the Monte Carlo approach are presented. The theoretical basis for calculating equilibrium properties of biological molecules by the Monte Carlo method is presented. Some of the st ...

A method for incorporating quantum mechanics into enzyme kinetics modeling is presented. Three aspects are emphasized: 1) combined quantum mechanical and molecular mechanical methods are used to represent the potential energy surface for modeling bond forming and breaking proc ...