Structural complexity, active sites reaction free energy

Figure 9 shows the theoretical transition state built into the active site of tyrosyl-tRNA synthetase, inferred from the crystal structure of the E-Tyr-AMP complex. Inspection of the active site reveals that there are no residues in position to participate in acid-base catalysis, so the crystal structure provided no obvious clues as to the reaction mechanism. However, analysis of the free energy... 

Another class of spatial multi-scale methods concerns the quantum chemistry community where efforts have been focussed on the combination of quantum mechanics (QM) methods with continuum electrostatic theories in order to realistically represent the solvation free energy in a polar environment. These methods have been refined over the years and can now give a reasonable description of solvation properties of an isotropic and homogeneous medium. However, these continuum models are not appropriate to represent the electrostatic and steric interactions of the structured environment with the active site. This is particularly true in the descriptions of complex systems like enzymes or catalysts. An appropriate description of such systems has been developed using a hybrid quantum mechanical/molecular mechanical (QM/MM) approaches where the QM methods are used to describe the active site where chemical reactions or electronic excitations occur, and MM methods are employed to capture the effect of the environment on the active site. 

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