A new methodology for the simulation of flexible protein-ligand interactions.
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.
Garner
James
J
Department of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia.
Deadman
John
J
Rhodes
David
D
Griffith
Renate
R
Keller
Paul A
PA
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
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D008024:Ligands; D011506:Proteins; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; C098320:efavirenz