Protein molecular models

Formulating proposed mechanisms of protein action requires investigating how proteins interact with ligands of all kinds, including other proteins. Molecular modeling programs allow the user to display and manipulate several... 

Molecular modelers thus put such quantitative work aside for a while. These molecular modelers were a new breed of theoretical chemist specializing in large biological molecules, especially proteins and nucleic acids. They worked at first with non-digital calculators. Such calculators would be used up to the early 1960s in laboratories like that of Gopalasamudram Ramachandran in India, who founded a major school of protein molecular modeling and elucidated the basic principles of stereochemistry about how proteins adopt their shapes. 

Photo 24 Linus Pauling working with a protein molecular model in the early 1950 s. The rectangular pieces of flat sheet metal represent the planar amide groups, so important in the structure of proteins (SP 105). The model represents Pauling and Corey s proposed structure for collagen (SP 103). 

The stereochemical outcome of the new FucA was indistinguishable compared to that obtained for the wild type. However, while the (J )-N-Cbz-aminoaldehydes yielded the anti(3i ,4i )-configured aldol adduct in high diastere-oselectivity (>2 98 syn iR,4-S)/anti(iR,4R) ratio), the (S) enantiomers depended on the aldehyde. In the extreme situation, R)-N-Chz prolinal derivatives ((J )-7a,b) gave exclusively the anti 3R,4-R) adduct whereas the S counterparts ((S)-7a,c,d) rendered the syn(3i ,4S) one. Protein molecular models were built to gain insight into the acceptor binding mode that led to this distinct stereochemical outcome [19]. 

Gilson, M. K. Multiple-site titration and molecular modeling Two rapid methods for computing energies and forces for ionizable groups in proteins. Proteins Struct. Punct. Genet. 15 (1993) 266-282. 

A. Neumaier, Molecular modeling of proteins and mathematical prediction of protein structure, SIAM Rev. 39 (1997), 407-460. 

In the late 1960s, Langridge and co-workers developed methods, first at Princeton, then at UC San Francisco, to visualize 3D molecular models on the screens of cathode-ray tubes. At the same time Marshall, at Washington University St. Louis, MO, USA, started visuaHzing protein structures on graphics screens. 

The visuahzation of hundreds or thousands of connected atoms, which are found in biological macromolecules, is no longer reasonable with the molecular models described above because too much detail would be shown. First of aU the models become vague if there are more than a few himdied atoms. This problem can be solved with some simplified models, which serve primarily to represent the secondary structure of the protein or nucleic acid backbone [201]. (Compare the balls and sticks model (Figure 2-124a) and the backbone representation (Figure 2-124b) of lysozyme.)... 

In order to represent 3D molecular models it is necessary to supply structure files with 3D information (e.g., pdb, xyz, df, mol, etc.. If structures from a structure editor are used directly, the files do not normally include 3D data. Indusion of such data can be achieved only via 3D structure generators, force-field calculations, etc. 3D structures can then be represented in various display modes, e.g., wire frame, balls and sticks, space-filling (see Section 2.11). Proteins are visualized by various representations of helices, / -strains, or tertiary structures. An additional feature is the ability to color the atoms according to subunits, temperature, or chain types. During all such operations the molecule can be interactively moved, rotated, or zoomed by the user. 

Mosimann S, S Meleshko and M N G Jones 1995. A Critical Assessment of Comparative Molecular Modeling of Tertiary Structures of Proteins. Proteins Structure, Function and Genetics 23 301-317. 

The biological properties of dioxin include an ability to bind to a protein known as the AH (aromatic hydrocarbon) receptor Dioxin IS not a hydrocarbon but it shares a certain structural property with aromatic hydrocarbons Try constructing molecular models of dioxin and anthracene to see these similarities... 

Protein Data Bank (Section 27 20) A central repository in which crystallographic coordinates for biological mole cules especially proteins are stored The data are accessi ble via the Worldwide Web and can be transformed into three dimensional images with appropriate molecular modeling software... 

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