computer modeling in molecular biology.pdf
computer modeling in molecular biology.pdf
computer modeling in molecular biology.pdf
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2.3.3 Available Modell<strong>in</strong>g Programs2 Modell<strong>in</strong>g Prote<strong>in</strong> Structures 29Homology modell<strong>in</strong>g programs of various degrees of automation are now readilyavailable. These <strong>in</strong>clude : Insight I1 [69] (commercial, graphics based, Homologymodell<strong>in</strong>g module: semi automatic); Quanta (commercial, graphics based, semiautomatic module) ; What If [70] (academic, graphics based, semi automaticmodule); 0 [71] (academic, graphics based, essentially crystallographic modell<strong>in</strong>gprogram but with database loop modell<strong>in</strong>g features); Sybyl (commercial, graphicsbased, semi automatic module based on Composer [72, 731, also available as a nongraphical,academic program). All these packages conta<strong>in</strong> essentially a sequencealignment program, a database loop search<strong>in</strong>g program and features for optimis<strong>in</strong>gside cha<strong>in</strong> conformations. For an assessment of the errors associated with suchmodell<strong>in</strong>g procedures see Topham et al. [63]. Such semi-automatic modell<strong>in</strong>gpackages can very quickly produce models with no bad atom-atom contacts butwhich are partially or completely wrong due to the errors associated with alignmentand loop build<strong>in</strong>g already discussed. Programs for evaluat<strong>in</strong>g homology models arenot generally <strong>in</strong>cluded <strong>in</strong> such packages: methods such as those described below(Section 2.4.2) should be used to look for errors. Regardless of the results of anytests, any user of models built <strong>in</strong> this way should always be m<strong>in</strong>dful of the likelyerrors.2.4 Modell<strong>in</strong>g de novo: Structure PredictionWhen no specific relationship can be found between a sequence of unknown structureand any known structure only direct structure prediction methods rema<strong>in</strong> an option,and as shown <strong>in</strong> Figure 2-1, only the secondary structure can be predicted withany degree of accuracy at present.2.4.1 A Family of Similar SequencesSecondary structure prediction (SSP) can carried out on s<strong>in</strong>gle sequences; however,where a family of homologous sequences exist more accurate results can be obta<strong>in</strong>ed.This has been known for some time [74, 751 but it is with the successful prediction[12] of the catalytic subunit of cyclic AMP dependent prote<strong>in</strong> k<strong>in</strong>ase [76] and thedevelopment of a neural-network based multiple sequence SSP method availableover the <strong>in</strong>ternet by e-mail [13, 141 that use of such methods have become
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