Lessons and Successes in the Use of Molecular Fields, an invited chapter for the ‘In Silico Drug Discovery Tools’ section of Comprehensive Medicinal Chemistry III, has recently been published by Elsevier. The chapter reviews more than thirty years of research in the area of molecular interaction fields, starting from the ground-breaking work done by Cramer, Goodford and Vinter, until the most recent applications to virtual screening, metabolism prediction, protein similarity across phylogenetically unrelated families and library design.
We believe that the reason for the longevity of molecular fields as computational chemistry workhorses is their capacity to provide a feature-rich description of molecular properties which is independent of the chemical structure. Encoding interaction properties through molecular fields inherently enables scaffold hopping, 3D similarity searches within large databases, ligand and protein structural alignment, cross-chemotype SAR elucidation.
All of the above tasks are the bread and butter of medicinal and computational chemists. Therefore, it is not surprising that over the years the creativity of researchers has built on top of the molecular field technology a number of blockbuster tools for computer-aided drug design, such as CoMFA, FieldScreen (now known as Blaze) or MetaSite, to name but a few. Thanks to their ‘core’ nature, as trends evolved and new needs emerged, fields have brilliantly managed to ride the ever changing waves of drug discovery, and are still at the forefront of the in silico armoury.
We take pride of having been among the lead actors on the molecular field stage, and we trust that readers will enjoy embarking on a fascinating journey through decades of field-based science as much as we did as authors.