Abstract
Protein motions, ranging from molecular flexibility to large-scale conformational change, play an essential role in many biochemical processes. Despite the explosion in our knowledge of structural and functional data, our understanding of protein movement is still very limited. In previous work, we developed and validated a motion planning based method for mapping protein folding pathways from unstructured conformations to the native state. In this paper, we propose a novel method based on rigidity theory to sample conformation space more effectively, and we describe extensions of our framework to automate the process and to map transitions between specified conformations. Our results show that these additions both improve the accuracy of our maps and enable us to study a broader range of motions for larger proteins. For example, we show that rigidity-based sampling results in maps that capture subtle folding differences between protein G and its mutations, NuG1 and NuG2, and we illustrate how our technique can be used to study large-scale conformational changes in calmodulin, a 148 residue signaling protein known to undergo conformational changes when binding to Ca2 + . Finally, we announce our web-based protein folding server which includes a publically available archive of protein motions: http://parasol.tamu.edu/foldingserver/
Supported in part by NSF Grants EIA-0103742, ACR-0081510, ACR-0113971, CCR-0113974, ACI-0326350, and by the DOE. Thomas supported in part by an NSF Graduate Research Fellowship.
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Thomas, S., Tang, X., Tapia, L., Amato, N.M. (2006). Simulating Protein Motions with Rigidity Analysis. In: Apostolico, A., Guerra, C., Istrail, S., Pevzner, P.A., Waterman, M. (eds) Research in Computational Molecular Biology. RECOMB 2006. Lecture Notes in Computer Science(), vol 3909. Springer, Berlin, Heidelberg. https://doi.org/10.1007/11732990_33
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DOI: https://doi.org/10.1007/11732990_33
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