Current Computer - Aided Drug Design - Volume 7, Issue 3, 2011

Almost all of today's recently released drugs are designed using Computer-Aided Drug Design (CADD) techniques. Among various methods, Structure-Based Design (SBD) and Pharmacophore Modeling are the two most successful methodologies in designing new drug candidates. Whereas SBD requires the receptor structure to be known, there is no such requirement for pharmacophore modeling. This makes phar Read More

The design of biological active compounds from the apoenzyme is still a challenging task. Herein a simple yet efficient technique is reported to generate a receptor based pharmacophore solely using a ligand-free protein crystal structure. Human leukocyte antigen-related phosphatase (PTP-LAR) is an apoenzyme and a receptor like transmembrane phosphatase that has emerged as a drug target for diabetes, obesity and can Read More

Generating a pharmacophore is often the first step towards understanding the interactions between a receptor and a ligand and can be pivotal to a successful drug discovery project. The pharmacophore tools at Accelrys have been used to assist in many different projects over the years, such as lead generation, scaffold hopping, mining ligand databases as well as many more. In this article, we will review the pharmacophore tools Read More

The intuitive nature of the pharmacophore concept has made it widely accepted by the medicinal chemistry community, evidenced by the past 3 decades of development and application of computerized pharmacophore modeling tools. On the other hand, shape complementarity has been recognized as a critical factor in molecular recognition between drugs and their receptors. Recent development of fast and accurate sh Read More

The question of how and why a small molecule binds to a protein is central to ligand-based drug discovery. The traditional way of approaching these questions is pharmacophore analysis. However, pharmacophores as usually applied lack quantitation and subtlety. An improvement is to consider the electrostatic and steric fields of the ligand directly. Molecular fields provide a rich view of the potential interactions that a molecule c Read More

The apparently paradoxical lack of correlation between the huge increase in the discovery of new potential drug targets made possible by the post-genomic sciences and new drugs development has stimulated many different interpretations. Here we illustrate the general principle of redundancy of biological pathways on hand of simplified mathematical approaches applied to different models of biological regulation. T Read More

AMP-activated protein kinase (AMPK) is an important therapeutic target for the potential treatment of metabolic disorders, cardiovascular disease and cancer. Recently, various classes of compounds that activate AMPK by direct or indirect interactions have been reported. The importance of computer-aided drug design approaches in the search for potent activators of AMPK is now established, including structure-based desig Read More