http://www.youtube.com/watch?v=fDevOumrquM&context=C3d49d1aADOEgsToPDskI9IY6BEyUIsShZLHjOg-9S
navigate to the link above for watching our first disordered protein seminar, presented by Aquila Dunn, Coskuner Group, UTSA.
Thursday, January 26, 2012
Sunday, January 22, 2012
http://www.annualreviews.org/doi/abs/10.1146/annurev.biophys.37.032807.125924?journalCode=biophys
Intrinsically disordered proteins (IDPs) lack stable tertiary and/or secondary structures under physiological conditions in vitro. They are highly abundant in nature and their functional repertoire complements the functions of ordered proteins. IDPs are involved in regulation, signaling, and control, where binding to multiple partners and high-specificity/low-affinity interactions play a crucial role. Functions of IDPs are tuned via alternative splicing and posttranslational modifications. Intrinsic disorder is a unique structural feature that enables IDPs to participate in both one-to-many and many-to-one signaling. Numerous IDPs are associated with human diseases, including cancer, cardiovascular disease, amyloidoses, neurodegenerative diseases, and diabetes. Overall, intriguing interconnections among intrinsic disorder, cell signaling, and human diseases suggest that protein conformational diseases may result not only from protein misfolding, but also from misidentification, missignaling, and unnatural or nonnative folding. IDPs, such as α-synuclein, tau protein, p53, and BRCA1, are attractive targets for drugs modulating protein-protein interactions. From these and other examples, novel strategies for drug discovery based on IDPs have been developed. To summarize work in this area, we are introducing the D2 (disorder in disorders) concept.
Intrinsically disordered proteins (IDPs) lack stable tertiary and/or secondary structures under physiological conditions in vitro. They are highly abundant in nature and their functional repertoire complements the functions of ordered proteins. IDPs are involved in regulation, signaling, and control, where binding to multiple partners and high-specificity/low-affinity interactions play a crucial role. Functions of IDPs are tuned via alternative splicing and posttranslational modifications. Intrinsic disorder is a unique structural feature that enables IDPs to participate in both one-to-many and many-to-one signaling. Numerous IDPs are associated with human diseases, including cancer, cardiovascular disease, amyloidoses, neurodegenerative diseases, and diabetes. Overall, intriguing interconnections among intrinsic disorder, cell signaling, and human diseases suggest that protein conformational diseases may result not only from protein misfolding, but also from misidentification, missignaling, and unnatural or nonnative folding. IDPs, such as α-synuclein, tau protein, p53, and BRCA1, are attractive targets for drugs modulating protein-protein interactions. From these and other examples, novel strategies for drug discovery based on IDPs have been developed. To summarize work in this area, we are introducing the D2 (disorder in disorders) concept.
Wednesday, January 18, 2012
Meeting
We will have a meeting on January 23 of 2012 that will be recorded and posted. The talks involve intrinsically disordered proteins in Parkinson's disease.
Saturday, January 14, 2012
Proteins and Metals
About one third of the proteins in the human body contain metals. Metalloproteins are essential for basic processes in life, such as DNA synthesis, detoxification, nitrogen, oxygen and carbon transportation. Despite their crucial roles in basic life processes, interactions of metals with proteins can also cause severe diseases and death. To avoid such detrimental interactions in the human body, treatments that involve metal ion chelators or other small organic molecules as drugs need to be designed and synthesized. However, effective studies that aim to design new treatments require knowledge about the coordination chemistry between the metal and protein as well as the structure of the metalloprotein. Our group investigates the coordination chemistry mechanisms of biological transition metal ions, such as copper, zinc and iron with intrinsically disordered proteins that are at the center of Alzheimer's and Parkinson's diseases, cancer, and cardiovascular diseases. We provide atomic level information with dynamics about the metalloprotein structures in solution. Even though all may sound easy, please know that these research activities are complex since it requires first the development of strategies and parameters using quantum mechanics and then the applications of statistical mechanics and thermodynamics. It is fun to develop new methods and techniques and/or parameters and then to apply these on metalloproteins, which may help to find more effective treatments to severe diseases. When you think about how many millions of people and their loved ones are affected by specific severe diseases, such as neurodegenerative diseases, it is worth to work hard with the hope that our studies can provide important milestones towards finding better treatments.
Wednesday, January 11, 2012
Tuesday, January 10, 2012
We wil be providing a workshop as part of the Expanding Your Horizons program on January 28, 2012! This program encourages girls in the 6th-8th grade to consider careers in science, technology, engineering, and math. To find out more about the program check out the link here!
Our recent study, Amyloid-β peptide structure in aqueous solution varies with fragment size, was published in the Journal of Chemical Physcis and selected for republication in the Virtual Journal of Biological Physics research. You can find the full paper here. The abstract for our paper is provided below as well. Enjoy!
Various fragment sizes of the amyloid-β (Aβ) peptide have been utilized to mimic the properties of the full-length Aβ peptide in solution. Among these smaller fragments, Aβ16 and Aβ28 have been investigated extensively. In this work, we report the structural and thermodynamic properties of the Aβ16, Aβ28, and Aβ42 peptides in an aqueous solution environment. We performed replica exchange molecular dynamics simulations along with thermodynamic calculations for investigating the conformational free energies, secondary and tertiary structures of the Aβ16, Aβ28, and Aβ42 peptides. The results show that the thermodynamic properties vary from each other for these peptides. Furthermore, the secondary structures in the Asp1-Lys16 and Asp1-Lys28 regions of Aβ42 cannot be completely captured by the Aβ16 and Aβ28 fragments. For example, the β-sheet structures in the N-terminal region of Aβ16 and Aβ28 are either not present or the abundance is significantly decreased in Aβ42. The α-helix and β-sheet abundances in Aβ28 and Aβ42 show trends – to some extent – with the potential of mean forces but no such trend could be obtained for Aβ16. Interestingly, Arg5 forms salt bridges with large abundances in all three peptides. The formation of a salt bridge between Asp23-Lys28 is more preferred over the Glu22-Lys28 salt bridge in Aβ28 but this trend is vice versa for Aβ42. This study shows that the Asp1-Lys16 and Asp1-Lys28 regions of the full length Aβ42 peptide cannot be completely mimicked by studying the Aβ16 and Aβ28 peptides.
Various fragment sizes of the amyloid-β (Aβ) peptide have been utilized to mimic the properties of the full-length Aβ peptide in solution. Among these smaller fragments, Aβ16 and Aβ28 have been investigated extensively. In this work, we report the structural and thermodynamic properties of the Aβ16, Aβ28, and Aβ42 peptides in an aqueous solution environment. We performed replica exchange molecular dynamics simulations along with thermodynamic calculations for investigating the conformational free energies, secondary and tertiary structures of the Aβ16, Aβ28, and Aβ42 peptides. The results show that the thermodynamic properties vary from each other for these peptides. Furthermore, the secondary structures in the Asp1-Lys16 and Asp1-Lys28 regions of Aβ42 cannot be completely captured by the Aβ16 and Aβ28 fragments. For example, the β-sheet structures in the N-terminal region of Aβ16 and Aβ28 are either not present or the abundance is significantly decreased in Aβ42. The α-helix and β-sheet abundances in Aβ28 and Aβ42 show trends – to some extent – with the potential of mean forces but no such trend could be obtained for Aβ16. Interestingly, Arg5 forms salt bridges with large abundances in all three peptides. The formation of a salt bridge between Asp23-Lys28 is more preferred over the Glu22-Lys28 salt bridge in Aβ28 but this trend is vice versa for Aβ42. This study shows that the Asp1-Lys16 and Asp1-Lys28 regions of the full length Aβ42 peptide cannot be completely mimicked by studying the Aβ16 and Aβ28 peptides.
Subscribe to:
Posts (Atom)