X-ray crystallography and molecular modeling

In contrast, the existence of peptide-carbohydrate mimicry is more surprising in that it is difficult to picture how these two different classes of compounds could mimic each other. The origin of this effect at the molecular level has been the subject of recent investigations by NMR spectroscopy, X-ray crystallography, and molecular modeling. In combination with functional data, these studies provide insight into the nature of this phenomenon. 

The dipeptide L-aspartyl-L-phenylalanine methyl ester (aspartamine) is about 200 times sweeter than sucrose. From conformational studies of this peptide and its derivatives, employing NMR, X-ray crystallography, and molecular modeling techniques, Goodman et at the University of Califor-... 

The initial coordinates r(0) are usually obtained from experimentally determined molecular structures, mainly from X-ray crystallography and NMR experiments. Alternatively, the initial coordinates can be based on computer models generated by a variety of modeling techniques (see Chapters 14 and 15). Note, however, that even the experimentally determined strucmres must often undergo some preparation steps before they can be used as initial structures in a dynamic simulation. 

More detailed aspects of protein function can be obtained also by force-field based approaches. Whereas protein function requires protein dynamics, no experimental technique can observe it directly on an atomic scale, and motions have to be simulated by molecular dynamics (MD) simulations. Also free energy differences (e.g. between binding energies of different protein ligands) can be characterised by MD simulations. Molecular mechanics or molecular dynamics based approaches are also necessary for homology modelling and for structure refinement in X-ray crystallography and NMR structure determination. 

The three-dimensional strucmres of Cro and of the lambda repressor protein have been determined by x-ray crystallography, and models for their binding and effecting the above-described molecular and genetic events have been proposed and tested. Both bind to DNA using hehx-turn-helix DNA binding domain motifs (see below). 

The electron diffraction analysis of l,2-bis(methylsulfonyl)ethane, CH3S02CH2CH2S02CH3 , yielded a limited amount of structural information. However, this substance has also been studied by X-ray crystallography , and the two sets of data offer a possibility for comparison. The molecular model is shown in Figure 14. 

We determined the structure of human PNP by x-ray crystallography and used these results in combination with computer-assisted molecular modeling to design inhibitor candidates. We examined how well the shape and chemical... 

Even though these approaches are powerful methods for determining functional sites on proteins, they are limited if not coupled with some form of structural determination. As Figure 2 illustrates, molecular biology and synthetic peptide/antibody approaches are not only interdependent, they are tied in with structural determination. Structural determination methods can take many forms, from the classic x-ray crystallography and NMR for three-dimensional determination, to two-dimensional methods such as circular dichroism and Fourier Transformed Infrared Spectroscopy, to predictive methods and modeling. A structural analysis is crucial to the interpretation of experimental results obtained from mutational and synthetic peptide/antibody techniques. 

Three cytotoxic peptides, patellamide D (31) and lissoclinamides 4-5 (32-33) were isolated from a Great Barrier Reef specimen of L. patella and identified by interpretation of spectral data. The peptides were found within the obligate algal symbiont of the genus Prochloron [65]. Another study of the same Australian L. patella reported lissoclinamide 6 (34), in addition to lissoclinamides 4-5 (32-33) and patellamide D (31). The structure of patellamide D (31) was obtained by X-ray crystallography and its conformation compared with those obtained by molecular modelling [66]. Patellamide D (31) has been reported to be a... 

We have used 2,7-disubstituted naphthyridines with hydroxy and amido groups to achieve a variety of molecular structures including M and P helices. A combination of X-ray crystallography and theoretical calculations on model compounds (B3LYP/6-31+G ) was used to discuss the tautomerism and the hydrogen bonds of compounds 106-111 [114], Compound 111 was used in the calculations instead of 108. 

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