Computational optimized geometries, importance

This is, however, an illustration of the importance of taking adsorbate deformations into account, and the usefulness of theoretical modelling for doing so. A computationally optimized 1 shifted adsorption geometry is shown in figure 5 (right), and this has an adsorbate orientation very close to the desired 45°, and not the simplistically expected 60°. Instead, the deformed 2 shift structure does not have a 45° orientation, but rather one of 35°. 

DHFR catalyzes the reduction of 7,8-dihydrofolate (H2F) to 5,6,7,8-tetrahydrofolate (H4F) using nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor (Fig. 17.1). Specifically, the pro-R hydride of NADPH is transferred stereospecifi-cally to the C6 of the pterin nucleus with concurrent protonation at the N5 position [1]. Structural studies of DHFR bound with substrates or substrate analogs have revealed the location and orientation of H2F, NADPH and the mechanistically important side chains [2]. Proper alignment of H2F and NADPH is crucial in enhancing the rate of the chemical step (hydride transfer). Ab initio, mixed quantum mechanical/molecular mechanical (QM/MM), and molecular dynamics computational studies have modeled the hydride transfer process and have deduced optimal geometries for the reaction [3-6]. The optimal C-C distance between the C4 of NADPH and C6 of H2F was calculated to be 2.7A [5, 6], which is significantly smaller than the initial distance of 3.34 A inferred from X-ray crystallography [2]. One proposed chemical mechanism involves a keto-enol tautomerization (Fig. 

Structure is the term applied here to specify the position in 3D space of the atomic nuclei in the minimum energy conformer of the analyzed species. The computer-assisted searching approach of the structure is called geometry optimization. The correcmess of geometry optimization is important because the value of some descriptors depends on the structure. 

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