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Overview
  QSite: A high-performance QM/MM program.
QSite applies quantum mechanics to the reactive center of a protein active site and molecular mechanics to the rest of the system. Its accuracy allows detailed understanding of reactions involving proteins, making it a powerful tool for lead optimization.


The Advantages of QM/MM methods.

Insight into reactive chemistry is crucial to understanding the mechanism of drug receptor interactions in systems where the ligand is covalently bound to the receptor. For example, it's necessary to study the transition states between bound and unbound forms in order to design antibiotics that are not subject to inactivation by beta lactamases. Classical molecular mechanics (MM) methods cannot describe the electronic changes during a reaction, and are ill-equipped to address ligand-receptor interactions in systems containing metals.

Ab initio quantum mechanics (QM) is required to study reactive chemistry or interactions involving transition metals in a protein environment. However, even with today's computer technology, full QM calculations of entire proteins are still intractable.

Mixed QM/MM calculations provide the ideal solution by separating out the reactive core, which can be accurately described with QM, while treating the remainder of the complex more efficiently with MM. While QM/MM may not be needed for every structure-based drug design project, many important systems cannot be effectively addressed by any other computational means. QM/MM is therefore a key component in the arsenal of computational drug discovery.

The active site of the oxy form of Hemerythrinis is shown in tubes while the protein backbone is represented by ribbons, the dioxygen that binds reversibly to Hemerythrin is drawn in spheres bonded to the iron atom on the right. The QSite-predicted in vivo free energy of binding of -5.2 kcal/mol is in remarkably good agreement with the experimental value of -7.3 kcal/mol, derived from the equilibrium constant of (2.5 ± 0.5)x10<sup>5</sup>M<sup>-1</sup> obtained from stopped-flow experiments carried out in solution.
The active site of the oxy form of Hemerythrinis is shown in tubes while the protein backbone is represented by ribbons, the dioxygen that binds reversibly to Hemerythrin is drawn in spheres bonded to the iron atom on the right. The QSite-predicted in vivo free energy of binding of -5.2 kcal/mol is in remarkably good agreement with the experimental value of -7.3 kcal/mol, derived from the equilibrium constant of (2.5 ± 0.5)x105M-1 obtained from stopped-flow experiments carried out in solution.
   Features
 
High performance: QSite outperforms other QM/MM programs because it takes advantage of Jaguar, long recognized as the industry leader in QM calculations.
Advanced technology: QSite's innovative approach to the QM/MM interface specifically addresses protein systems and interactions between QM and MM regions. QSite also models crucial solvation effects.
Transition metal convergence: QSite achieves unparalleled accuracy in metalloproteins thanks to Jaguar's advanced capabilities; it reliably and efficiently converges to the correct ground state of transition metal containing systems.
Wavefunction choices: QSite offers different levels of theory to evaluate the QM region: Hartree Fock, DFT, and local MP2. This allows the user to choose the best balance between computational cost and accuracy.
Advanced calculation setup and analysis: QSite automatically applies special interface parameters, making it simple to set up calculations. Computed results, such as molecular orbitals and electron densities, can be visualized within Maestro.
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