A high-performance QM/MM program
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.
QSite outperforms other QM/MM programs because it takes advantage of Jaguar, long recognized as the industry leader in QM calculations.
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.
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.
Citations and Acknowledgements
Schrödinger Release 2017-1: QSite, Schrödinger, LLC, New York, NY, 2017.
Murphy, R. B.; Philipp, D. M.; Friesner, R. A., "A mixed quantum mechanics/molecular mechanics (QM/MM) method for large-scale modeling of chemistry in protein environments," J. Comp. Chem., 2000, 21, 1442-1457
Philipp, D. M.; Friesner, R. A., "Mixed ab initio QM/MM modeling using frozen orbitals and tests with alanine dipeptide and tetrapeptide," J. Comp. Chem., 1999, 20, 1468-1494