Diamond lattice model

Conformational analysis has been used to find and predict conformations which maximize antibiotic activity, using x-ray crystal stmctures coupled with nmr and cd spectra. An early approach utilized the Dale diamond lattice conformational model (480), which was extended to other diamond lattice models (472,481—483). Other studies have reHed on nmr data (225,484—491). However, extensive correlations between conformation and biological activity have not been successful (486,492). 

HLADH converts a wide range of substrates. For the predicition of the stereoselectivity of reduction reactions, originally Prelog s diamond lattice model was applied, which is based upon the characteristic properties of the ADH of Curvularia falcata [37]. This model describes the stereospecificity of HLADH catalyzed reductions of simple acyclic substrates such as aldehydes. Later on, for more complex acyclic and cyclic substrates, a cubic-space model of the active site was developed [38,121]. Other models are based upon symmetric properties [122-125] or upon a refined diamond lattice model [126-129]. 

The diamond lattice model (Figure 7) was developed using six-membered ring ketone substrates. The determination of forbidden and undesirable positions was achieved by analysis of the relative rates of reduction of a series of cyclohexanones and decalones of known absolute configuration. The geometry indicated at the C-0 centre was considered to resemble the structure of the alcohol rather than that of the ketone in the transition state. It was assumed that all substrate molecules bound with oxygen in the... 

Horjales and Branden (1985) constructed a diamond lattice model by docking cyclohexanol and its monoethyl derivatives into the experimentally determined active site of the enzyme (X-ray crystallographic structure, 1982), using computer graphics and energy minimization methods. The lattice positions were classified as allowed, forbidden or boundary depending their distances to protein atoms (Figure 8). The... 

Figure 9. Figure 9a A comparison between two diamond lattice models. Positions A-J are derived by kinetic studies as forbidden or hindered. Positions K-R represent boundary or forbidden positions defined by Horjales and Branden. Figure 9b shows the extended diamond lattice model.

The diamond lattice representation of a protein, while reasonable for idealized models of / and a proteins, cannot reproduce the chain geometry of more complex motifs such as a// proteins. To remove this fundamental limitation, the chess-knight model [54] of the protein backbone was developed. In contrast to a diamond lattice model, it allows all possible protein folding motifs to be represented at low resolution [121]. The force field requirements for a unique native state are essentially the same in this finer lattice representation as for diamond lattice models. 

Continuous models of minimal / sheets have been investigated by Monte Carlo simulated annealing [128] and by Brownian dynamics [23,52, 53,129]. The design of the / -barrel geometry and the essential features of the force field are complementary to the diamond lattice models of Skolnick... 

In order to predict the stereochemical outcome of HLADH-catalyzed reductions, a number of models have been developed, each of which having its own merits. The first rationale emerged from the diamond lattice model of V. Prelog, which was originally developed for Curvularia falcata [798]. A more recently developed... 

The correlation time p characterizes three-bond jumps, and the correlation time B characterizes other processes. Bendler and Yaris have also reconsidered the diamond lattice model, and replaced the discrete jump kinetic formulation by a continuum with adjustable cut-offs in the frequency spectrum. The high cut-off arises from the finite size of the smallest displaceable unit, and the low cut-off from the fact that chain displacements will be damped out as they travel down the chain. Librational motions, hitherto neglected, have been considered by Howarth, with success in interpreting relaxation data on proteins. It is possible that this factor should also be taken into account for synthetic polymers. 

Highly simplified models of protein structure embedded into low coordination lattices have been used for tertiary structure prediction for almost 20 years [65, 66, 75]. For example, Covell and Jemigan [64] enumerated all possible conformations of five small proteins restricted to fee and bcc lattices. They found that the nativelike conformation always has an energy within 2% of the lowest energy. Virtually simultaneously. Hinds and Levitt [28] used a diamond lattice model where a single lattice unit represents several residues. While such a representation cannot reproduce the geometric details of helices or P-sheets, the topology of native folds could be recovered with moderate accuracy. 

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