title: In silico fragment-based drug design.
abstract: BACKGROUND
  In silico fragment-based drug design (FBDD) is a relatively new approach inspired by the success of the biophysical fragment-based drug discovery field. Here, we review the progress made by this approach in the last decade and showcase how it complements and expands the capabilities of biophysical FBDD and structure-based drug design to generate diverse, efficient drug candidates.
  
  
  METHODS
  Advancements in several areas of research that have enabled the development of in silico FBDD and some applications in drug discovery projects are reviewed.
  
  
  RESULTS
  The reader is introduced to various computational methods that are used for in silico FBDD, the fragment library composition for this technique, special applications used to identify binding sites on the surface of proteins and how to assess the druggability of these sites. In addition, the reader will gain insight into the proper application of this approach from examples of successful programs.
  
  
  CONCLUSIONS
  In silico FBDD captures a much larger chemical space than high-throughput screening and biophysical FBDD increasing the probability of developing more diverse, patentable and efficient molecules that can become oral drugs. The application of in silico FBDD holds great promise for historically challenging targets such as protein-protein interactions. Future advances in force fields, scoring functions and automated methods for determining synthetic accessibility will all aid in delivering more successes with in silico FBDD.
authors: Ansaris, Four Valley Square, 512 East Township Line Road, Blue Bell, PA 19422, USA. zkonteatis@ansarisbio.com
authors: Zenon D
authors: ZD
authors: Konteatis
mesh_terms: D000818:Animals; D001665:Binding Sites; D001703:Biophysics; D019295:Computational Biology; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology*; D019151:Peptide Library; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000187:drug effects; D012984:Software
chemical_list: D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D019151:Peptide Library; D043562:Receptors, G-Protein-Coupled