Enhancing the accuracy of virtual screening: molecular dynamics with quantum-refined force fields.
A methodology aimed at improving the accuracy of current docking-scoring procedures is proposed, and validated through detailed tests of its performance in predicting the activity of HIV-1 protease inhibitors. This methodology is based on molecular dynamics simulations using a force field whose effective charges are refined by means of a novel procedure that relies on quantum-mechanical calculations and preserves the internal consistency of the parameterization scheme.
Curioni
Alessandro
A
IBM Research, Zurich Research Laboratory, Rüschlikon, Switzerland. cur@zurich.ibm.com
Mordasini
Tiziana
T
Andreoni
Wanda
W
D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D008024:Ligands; D015394:Molecular Structure; D011506:Proteins / Q000737:chemistry; D011789:Quantum Theory; D013816:Thermodynamics; D014584:User-Computer Interface
D017320:HIV Protease Inhibitors; D008024:Ligands; D011506:Proteins