Confronting the problem of interconnected structural changes in the comparative modeling of proteins.

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TitleConfronting the problem of interconnected structural changes in the comparative modeling of proteins.
Publication TypeJournal Article
Year of Publication1995
AuthorsSamudrala, R, Pedersen, JT, Zhou, HB, Luo, R, Fidelis, K, Moult, J
Date Published1995 Nov
KeywordsAmino Acid Sequence, Bacterial Proteins, Computer Simulation, Eosinophil-Derived Neurotoxin, Information Systems, Models, Molecular, Molecular Sequence Data, Neurotoxins, Phosphoenolpyruvate Sugar Phosphotransferase System, Protein Conformation, Receptors, Retinoic Acid, Ribonucleases, Sequence Alignment, Sequence Deletion, Software, Templates, Genetic

Comparative models of three proteins have been built using a variety of computational methods, heavily supplemented by visual inspection. We consider the accuracy obtained to be worse than expected. A careful analysis of the models shows that a major reason for the poor results is the interconnectedness of the structural differences between the target proteins and the template structures they were modeled from. Side chain conformations are often determined by details of the structure remote in the sequence, and can be influenced by relatively small main chain changes. Almost all of the regions of substantial main chain conformational change interact with at least one other such region, so that they often cannot be modeled independently. Visual inspection is sometimes effective in correcting errors in sequence alignment and in spotting when an alternative template structure is more appropriate. We expect some improvements in the near future through the development of structure-based sequence alignment tools, side chain interconnectedness rotamer choice algorithms, and a better understanding of the context sensitivity of conformational features.

Alternate JournalProteins
PubMed ID8710826
Grant ListGM41034 / GM / NIGMS NIH HHS / United States