title: VAMMPIRE-LORD: a web server for straightforward lead optimization using matched molecular pairs.
abstract: VAMMPIRE-LORD (lead optimization by rational design) describes an innovative strategy to improve the binding affinity of a defined lead compound using 3D matched molecular pairs (3D-MMPs). 3D-MMPs are defined as pairs of molecules that differ in exactly one structural transformation and have a known bioactive conformation. We developed a novel atom-pair descriptor (LORD_FP) that represents the ligand-as well as the receptor environment-of a chemical transformation and built a predictive model based on 17602 3D-MMPs. We demonstrate that the created model is able to extrapolate the knowledge of a chemical transformation and the associated effect on ligand affinity to any similar system. VAMMPIRE-LORD was implemented as a web server that guides the user step-by-step through the optimization process of a defined lead compound.
authors: Institute of Pharmaceutical Chemistry, Goethe University , Frankfurt 60438, Germany.
authors: Julia
authors: J
authors: Weber
authors: Janosch
authors: J
authors: Achenbach
authors: Daniel
authors: D
authors: Moser
authors: Ewgenij
authors: E
authors: Proschak
mesh_terms: D000465:Algorithms; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000494:pharmacology; D062126:Databases, Chemical; D055808:Drug Discovery / Q000295:instrumentation / Q000379:methods*; D005544:Forecasting; D020407:Internet / Q000295:instrumentation*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D008024:Ligands