کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2190020 1096231 2006 18 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structure-based Prediction of bZIP Partnering Specificity
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Structure-based Prediction of bZIP Partnering Specificity
چکیده انگلیسی

Predicting protein interaction specificity from sequence is an important goal in computational biology. We present a model for predicting the interaction preferences of coiled–coil peptides derived from bZIP transcription factors that performs very well when tested against experimental protein microarray data. We used only sequence information to build atomic-resolution structures for 1711 dimeric complexes, and evaluated these with a variety of functions based on physics, learned empirical weights or experimental coupling energies. A purely physical model, similar to those used for protein design studies, gave reasonable performance. The results were improved significantly when helix propensities were used in place of a structurally explicit model to represent the unfolded reference state. Further improvement resulted upon accounting for residue–residue interactions in competing states in a generic way. Purely physical structure-based methods had difficulty capturing core interactions accurately, especially those involving polar residues such as asparagine. When these terms were replaced with weights from a machine-learning approach, the resulting model was able to correctly order the stabilities of over 6000 pairs of complexes with greater than 90% accuracy. The final model is physically interpretable, and suggests specific pairs of residues that are important for bZIP interaction specificity. Our results illustrate the power and potential of structural modeling as a method for predicting protein interactions and highlight obstacles that must be overcome to reach quantitative accuracy using a de novo approach. Our method shows unprecedented performance in predicting protein–protein interaction specificity accurately using structural modeling and suggests that predicting coiled–coil interactions generally may be within reach.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 355, Issue 5, 3 February 2006, Pages 1125–1142
نویسندگان
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