Abstract: Combined QM/MM methods provide an accurate and efficient
energetic description of complex chemical and biological systems,
leading to significant advances in the understanding of chemical
reactions in solution and in enzymes.  Ab initio QM/MM methods
capitalize on the accuracy and reliability of the associated quantum
mechanical approaches, however at a much higher computational cost
compared with semiempirical quantum mechanical approaches. Thus
reaction path and activation free energy calculations encounter unique
challenges in simulation timescales and phase space sampling. Recent
developments of the QM/MM minimum free energy path method overcome
these challenges and enable accurate free energy determination for
reaction and redox processes in solution and enzymes. Applications to
several solution and enzyme reactions and redox processes will also be
highlighted.

We have developed an approach to detect non-covalent interactions in
real space, based on the electron density and its derivatives. The
intricate non-covalent interactions that govern many areas of biology
and chemistry are not easily identified from molecular structure. Our
approach reveals underlying chemistry that compliments the covalent
structure.  It provides a rich representation of van der Waals
interactions, hydrogen bonds, and steric repulsion in small molecules,
molecular complexes, and solids.

References:

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Methodology and application to triosephosphate isomerase," Journal of
Chemical Theory and Computation, vol. 3, pp. 390-406, 2007
H. Hu, Z. Y. Lu, J. M. Parks, S. K. Burger, and W. T. Yang, "Quantum
mechanics/molecular mechanics minimum free-energy path for accurate
reaction energetics in solution and enzymes: Sequential sampling and
optimization on the potential of mean force surface," Journal of
Chemical Physics, vol. 128, p. 034105, 2008
H. Hu and W. T. Yang, "Free energies of chemical reactions in solution
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methods," Annual Review of Physical Chemistry, vol. 59, pp. 573-601,
2008
X. C. Zeng, H. Hu, X. Q. Hu, and W. T. Yang, "Calculating solution
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X. Hu, H. Hu, J. A. Melvin, K. W. Clancy, D. G. McCafferty, and W. T.
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