Harder,better,faster,stronger: large-scale QM/MM

Computational prediction of enzyme mechanism and protein function requires accurate physics-based models and suitable sampling. We discuss recent advances in large-scale quantum mechanical (QM) modeling of biochemical systems that have reduced the cost of high-accuracy models. Tradeoffs between sampling and accuracy have motivated modeling with molecular mechanics (MM) in a multiscale QM/MM or iterative approach. Limitations to both conventional density-functional theory and classical MM force fields remain for describing noncovalent interactions in comparison to experiment or wavefunction theory. Because predictions of enzyme action (i.e. electrostatics), free energy barriers, and mechanisms are sensitive to the protocol and embedding method in QM/MM, convergence tests and systematic methods for quantifying QM-level interactions are a needed, active area of development.

Check out our recent invited Current Opinion in Structural Biology article on the topic ! It's part of the 2022 special issue on Theory Simulation/Computational Methods edited by Qiang Cui and Michelle McCully!

About Us

The Kulik group focuses on the development and application of new electronic structure methods and atomistic simulations tools in the broad area of catalysis.

Our Interests

We are interested in transition metal chemistry, with applications from biological systems (i.e. enzymes) to nonbiological applications in surface science and molecular catalysis.

Our Focus

A key focus of our group is to understand mechanistic features of complex catalysts and to facilitate and develop tools for computationally driven design.

Contact Us

Questions or comments? Let us know! Contact Dr. Kulik: