Structure-based drug design: from nucleic acid to membrane protein targets.
The in silico methods for drug discovery are becoming increasingly powerful and useful. That, in combination with increasing computer processor power, in our case using a novel distributed computing grid, has enabled us to greatly enhance our virtual screening efforts. Herein we review some of these efforts using both receptor and ligand-based virtual screening, with the goal of finding new anti-cancer agents. In particular, nucleic acids are a neglected set of targets, especially the different morphologies of duplex, triplex, and quadruplex DNA, many of which have increasing biological relevance. We also review examples of molecular modeling to understand receptors and using virtual screening against G-protein coupled receptor membrane proteins.
Dailey
Magdalena M
MM
Department of Chemistry, University of Louisville, Louisville, KY 40292, USA.
Hait
Chayanendu
C
Holt
Patrick A
PA
Maguire
Jon M
JM
Meier
Jason B
JB
Miller
M Clarke
MC
Petraccone
Luigi
L
Trent
John O
JO
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D003198:Computer Simulation; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000706:statistics & numerical data; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry / Q000187:drug effects*; D008958:Models, Molecular; D015394:Molecular Structure; D009696:Nucleic Acids / Q000737:chemistry / Q000187:drug effects*; D025481:Phosphofructokinase-2 / Q000037:antagonists & inhibitors / Q000737:chemistry; D010750:Phosphoproteins / Q000737:chemistry / Q000187:drug effects; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000737:chemistry / Q000187:drug effects; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000737:chemistry; D014584:User-Computer Interface; D000097796:Nucleolin
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D008263:Macrophage Migration-Inhibitory Factors; D008565:Membrane Proteins; D009696:Nucleic Acids; D025481:Phosphofructokinase-2; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D019718:Receptors, CXCR4; D019098:Telomerase; D000097796:Nucleolin; C527276:CXCR4 protein, human