Intrinsically Disordered Proteins: Where Computation Meets Experiment
Proteins are heteropolymers that play important roles in virtually every biological reaction. While many proteins have well-defined three-dimensional structures that are inextricably coupled to their function, intrinsically disordered proteins (IDPs) do not have a well-defined structure, and it is t...
| Main Authors: | , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
MDPI AG
2014
|
| Online Access: | http://hdl.handle.net/1721.1/92517 https://orcid.org/0000-0002-3415-242X https://orcid.org/0000-0002-8612-4797 https://orcid.org/0000-0002-8639-1860 |
| _version_ | 1826207518211178496 |
|---|---|
| author | Burger, Virginia M. Gurry, Thomas Stultz, Collin M. |
| author2 | Institute for Medical Engineering and Science |
| author_facet | Institute for Medical Engineering and Science Burger, Virginia M. Gurry, Thomas Stultz, Collin M. |
| author_sort | Burger, Virginia M. |
| collection | MIT |
| description | Proteins are heteropolymers that play important roles in virtually every biological reaction. While many proteins have well-defined three-dimensional structures that are inextricably coupled to their function, intrinsically disordered proteins (IDPs) do not have a well-defined structure, and it is this lack of structure that facilitates their function. As many IDPs are involved in essential cellular processes, various diseases have been linked to their malfunction, thereby making them important drug targets. In this review we discuss methods for studying IDPs and provide examples of how computational methods can improve our understanding of IDPs. We focus on two intensely studied IDPs that have been implicated in very different pathologic pathways. The first, p53, has been linked to over 50% of human cancers, and the second, Amyloid-β (Aβ), forms neurotoxic aggregates in the brains of patients with Alzheimer’s disease. We use these representative proteins to illustrate some of the challenges associated with studying IDPs and demonstrate how computational tools can be fruitfully applied to arrive at a more comprehensive understanding of these fascinating heteropolymers. |
| first_indexed | 2024-09-23T13:50:48Z |
| format | Article |
| id | mit-1721.1/92517 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:50:48Z |
| publishDate | 2014 |
| publisher | MDPI AG |
| record_format | dspace |
| spelling | mit-1721.1/925172022-10-01T17:28:24Z Intrinsically Disordered Proteins: Where Computation Meets Experiment Burger, Virginia M. Gurry, Thomas Stultz, Collin M. Institute for Medical Engineering and Science Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology. Research Laboratory of Electronics Burger, Virginia M. Gurry, Thomas Stultz, Collin M. Proteins are heteropolymers that play important roles in virtually every biological reaction. While many proteins have well-defined three-dimensional structures that are inextricably coupled to their function, intrinsically disordered proteins (IDPs) do not have a well-defined structure, and it is this lack of structure that facilitates their function. As many IDPs are involved in essential cellular processes, various diseases have been linked to their malfunction, thereby making them important drug targets. In this review we discuss methods for studying IDPs and provide examples of how computational methods can improve our understanding of IDPs. We focus on two intensely studied IDPs that have been implicated in very different pathologic pathways. The first, p53, has been linked to over 50% of human cancers, and the second, Amyloid-β (Aβ), forms neurotoxic aggregates in the brains of patients with Alzheimer’s disease. We use these representative proteins to illustrate some of the challenges associated with studying IDPs and demonstrate how computational tools can be fruitfully applied to arrive at a more comprehensive understanding of these fascinating heteropolymers. National Science Foundation (U.S.). Directorate for Biological Sciences. Postdoctoral Research Fellowship (Grant 1309247) 2014-12-24T19:16:10Z 2014-12-24T19:16:10Z 2014-10 2014-10 Article http://purl.org/eprint/type/JournalArticle 2073-4360 http://hdl.handle.net/1721.1/92517 Burger, Virginia M., Thomas Gurry, and Collin M. Stultz. “Intrinsically Disordered Proteins: Where Computation Meets Experiment.” Polymers 6, no. 10 (October 2014): 2684–2719. https://orcid.org/0000-0002-3415-242X https://orcid.org/0000-0002-8612-4797 https://orcid.org/0000-0002-8639-1860 en_US http://dx.doi.org/10.3390/polym6102684 Polymers Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf MDPI AG MDPI Publishing |
| spellingShingle | Burger, Virginia M. Gurry, Thomas Stultz, Collin M. Intrinsically Disordered Proteins: Where Computation Meets Experiment |
| title | Intrinsically Disordered Proteins: Where Computation Meets Experiment |
| title_full | Intrinsically Disordered Proteins: Where Computation Meets Experiment |
| title_fullStr | Intrinsically Disordered Proteins: Where Computation Meets Experiment |
| title_full_unstemmed | Intrinsically Disordered Proteins: Where Computation Meets Experiment |
| title_short | Intrinsically Disordered Proteins: Where Computation Meets Experiment |
| title_sort | intrinsically disordered proteins where computation meets experiment |
| url | http://hdl.handle.net/1721.1/92517 https://orcid.org/0000-0002-3415-242X https://orcid.org/0000-0002-8612-4797 https://orcid.org/0000-0002-8639-1860 |
| work_keys_str_mv | AT burgervirginiam intrinsicallydisorderedproteinswherecomputationmeetsexperiment AT gurrythomas intrinsicallydisorderedproteinswherecomputationmeetsexperiment AT stultzcollinm intrinsicallydisorderedproteinswherecomputationmeetsexperiment |