Editorial [Hot Topic: Computer Aided Drug Design (Executive Editor: M. Rami Reddy)]

Advances in protein crystallography and molecular simulations have greatly aided computer aided drug design paradigms and the accuracy of binding affinity predictions. The methods used in the discovery and / or optimization of a lead inhibitor have ranged from graphical visualization of the ligand in the binding site to calculation of relative binding affinities using molecular dynamics simulations in conjunction with the Free Energy Perturbation (FEP) approach. The aim of the Computer Aided Drug Design (CADD) issue of Current Pharmaceutical Design is to provide computational chemists and medicinal chemists with a comprehensive review of the methods used for drug design. While the FEP approach remains the method that consistently generates the most accurate free energies, its high CPU requirements and inability to evaluate compounds that differ significantly in structure, clearly limit the impact and value of FEP calculations on drug design. Accordingly, efforts are ongoing to develop faster methods such as high-throughput docking, molecular mechanics methods, etc. that have the potential to evaluate a large number of compounds qualitatively. The first article focuses on lead inhibitor optimization strategies using the free energy perturbation approach and molecular mechanics methods and evaluates the merits of each method for predicting relative binding affinities of fructose 1,6- bisphosphatase inhibitors. The second article summarizes all the published structural information for matrix metalloprotease inhibitor complexes and the design of specific matrix metalloproteinase inhibitors using structure-based drug design methods. The third article focuses on various computational aspects of docking-based virtual screening of small molecule databases. In addition the article discusses the fundamental issues and challenges associated with various docking methods. The fourth article describes several computational techniques such as high-throughput docking and similarity searching to identify potential lead MurB inhibitors. The fifth article describes computer-based strategies for modeling the interaction of agouti-related protein (AGRP) and related peptide ligands with the AGRP-binding site of murine melanocorin receptors. The final article describes efforts to design and prepare fumagillin and curcumin analogs and the antiangiogenic activities for a promising anti-cancer treatment discovered using CADD methods. Overall, this issue provides an extensive overview of the scope and limitations of CADD methods. The authors contributing to this issue are well-recognized leaders in this field of research representing both academic institutions and pharmaceutical industry. As an Executive Editor of Current Pharmaceutical Design, I would like to thank the authors for their contributions. I would also like to thank Dr. Mark Erion for his helpful suggestions and his encouragement and support in editing this CADD issue.