Protein Structure and Function: Application of Bioinformatics Methods - John Rigden 2014

Prediction of Membrane Protein Structure
Future Prospects for Membrane Protein Structure Prediction Methods

Despite the successful application of ROSETTA and FILM, numerous limitations inherent to these Methods must be addressed in the future. Currently, the primary limitation is the difficulty in handling large transmembrane structures. The Combinatorial Nature of ab initio methods makes them computationally cumbersome and unsuitable for studying structures exceeding 150 Amino Acids in size. There are several ways to overcome this limitation. The simplest approach, applicable to FILM, involves generating smaller fragment libraries of super-secondary structures that contain exclusively membrane protein structures. In this case, fragment searching is performed among Conformations that constitute parts of large transmembrane structures. Further method improvement can be achieved by replacing simple supercoiled motifs with larger structural fragments. Enhancements to ROSETTA that will enable its application for predicting The Structure of large domains rely on developing advanced conformation Selection methods and finding ways to more accurately account for Electrostatic Interactions.