computer modeling in molecular biology.pdf

2 Modelling Protein Structures 31specified in a protein chain. No method for identifying such sequences directly hasyet been developed but it would seem clear that many sequences that are compatiblewith the desired final fold may contain no such folding signals. Until an understandingof the requirements for such sites is developed, de novo protein design [89] willremain very difficult, particularly for large proteins.2.5 Future PossibilitiesThis review has tried to present a snapshot of what is possible now. What are theprospects for the near future?Research is most active in the area of threading. The many groups developingpotentials for fold recognition have taken a number of slightly different approaches,each with its own advantages. There will be more variations and those in the fieldanticipate substantial further improvements in the potentials. Fold recognition ishowever only the first stage in building a 3-D model.Threading methods should ultimately be able to incorporate almost all themethods discussed for model building and evaluation so that a single sequence (Section2.4.2) may be tested against all known folds. It is therefore anticipated that whatwill emerge will not only provide more accurate fold recognition, but the incorporationof other, more detailed, model-building techniques to produce a specific threedimensionalstructural prediction. It is by bringing together the various techniquesfor prediction and testing of structures that the interaction between them willultimately generate the most satisfactory results.2.6 SummaryThe explosion of protein sequence and structural information has generated in itswake a number of significant advances in protein modelling methods. If a relationshipcan be demonstrated between the sequence to be modelled and some knownstructure, a 3-D model of predictable quality can be constructed. If no such relationshipcan be shown, models can still be constructed but with little quantification ofthe chance of their being correct.