Strategies for protein structure model generation

Abstract: This chapter deals with approaches for protein three-dimensional structure prediction, starting out from a single input sequence with unknown struc- ture, the 'query' or 'target' sequence. Both template based and template free modelling techniques are treated, and how resulting structural models may be selected and refined. We give a concrete flowchart for how to de- cide which modelling strategy is best suited in particular circumstances, and which steps need to be taken in each strategy. Notably, the ability to locate a suitable structural template by homology or fold recognition is crucial; without this models will be of low quality at best. With a template avail- able, the quality of the query-template alignment crucially determines the model quality. We also discuss how other, courser, experimental data may be incorporated in the modelling process to alleviate the problem of missing template structures. Finally, we discuss measures to predict the quality of models generated.