Computer programs, protein structure analysis

Selected entries from Methods in Enzymology [vol, page(s)] Analysis of GTP-binding/GTPase cycle of G protein, 237, 411-412 applications, 240, 216-217, 247 246, 301-302 [diffusion rates, 246, 303 distance of closest approach, 246, 303 DNA (Holliday junctions, 246, 325-326 hybridization, 246, 324 structure, 246, 322-324) dye development, 246, 303, 328 reaction kinetics, 246, 18, 302-303, 322] computer programs for testing, 240, 243-247 conformational distribution determination, 240, 247-253 decay evaluation [donor fluorescence decay, 240, 230-234, 249-250, 252 exponential approximation of exact theoretical decay, 240, 222-229 linked systems, 240, 234-237, 249-253 randomly distributed fluorophores, 240, 237-243] diffusion coefficient determination, 240, 248, 250-251 diffusion-enhanced FRET, 246, 326-328 distance measurement [accuracy, 246, 330 effect of dye orientation, 246, 305, 312-313 limitations, 246,... 

For new or would-be users of models, I present in Chapter 11 an introduction to molecular modeling, demonstrating how modern graphics programs allow users to display and manipulate models and to perform powerful structure analysis, even on desktop computers. This chapter also provides information on how to use the World Wide Web to obtain graphics programs and learn how to use them. It also provides an introduction to the Protein Data Bank (PDB), a World Wide Web resource from which you can obtain most of the available macromolecular models. 

Glucagon is one of the few small proteins on which a normal-mode analysis has been done (Tasumi et al., 1982). It contains 29 amino acid residues, and its structure has been determined to 3 A resolution (Bernstein et al., 1977). The force field used in the calculation was that refined for a side-chain point-mass approximation (Dwivedi and Krimm, 1984b). The computer program was one specifically designed to handle such large molecules (Tasumi et al., 1982). At the time it could not include hydrogen bonds, but more recent versions are able to do so (Ataka and Tasumi, 1986). The present results must, therefore, be taken as mainly illustrative. 

In the light of all of these considerations, perhaps the most important frontier is a conceptual one. As the access to structural information increases, along with convenient computer programs that can be used to visualize and analyze complex biomolecules, it is hoped that more chemists will see proteins as the organic molecules that they are. The principles of chemical reactivity and conformational analysis apply to these compounds just as they do to any other natural product, and many groups have used exactly these same concepts to develop the reactions described herein. The development of future methods to meet the above challenges will be achieved most successfully by those who have adopted this mindset. 

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