title: A new methodology for the simulation of flexible protein-ligand interactions.
abstract: A methodology has been developed for the simulation of induced fit between a ligand and its target protein. It utilizes constrained molecular dynamics where atoms determined to be immobile from difference distance matrix studies are fixed. Application of this methodology to HIV-1 reverse transcriptase (RT) as the example target protein has demonstrated its robustness. Short simulation times are sufficient to achieve good refinement of docking poses resulting from exchange of structurally dissimilar inhibitors between crystal structures.
authors.affiliation: Department of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Garner
authors.forename: John
authors.initials: J
authors.lastname: Deadman
authors.forename: David
authors.initials: D
authors.lastname: Rhodes
authors.forename: Renate
authors.initials: R
authors.lastname: Griffith
authors.forename: Paul A
authors.initials: PA
authors.lastname: Keller
mesh_terms: D000480:Alkynes; D048588:Benzoxazines / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D003521:Cyclopropanes; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics; D008024:Ligands; D008958:Models, Molecular; D019829:Nevirapine / Q000737:chemistry; D017354:Point Mutation; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D008024:Ligands; D011506:Proteins; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; C098320:efavirenz