Bulletin of the American Physical Society
Annual Meeting of the APS Four Corners Section
Volume 60, Number 11
Friday–Saturday, October 16–17, 2015; Tempe, Arizona
Session K9: Biological Physics VI: Protein Structure |
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Chair: Rick Kirian, Arizona State University Room: PSA106 |
Saturday, October 17, 2015 1:12PM - 1:36PM |
K9.00001: Large-scale simulations of molecular machines: the ribosome Invited Speaker: Karissa Sanbonmatsu The ribosome plays a central role in all life forms and is responsible for protein synthesis. Here, the ribosome must read the genetic information and implement this information by producing the corresponding proteins. Approximately 50% of the antibiotic drugs used in US hospitals function by targeting the ribosome. Mechanistic understanding of ribosome activity will aid in the design of new antibiotics that combat the growing 'superbug' problem in today's hospitals. Over the past decade, we have focused on the mechanism by which the ribosome decodes genetic information ('the decoding problem', or 'tRNA selection'). By performing large-scale molecular dynamics simulations of the ribosome, we are able to examine the inner workings of this molecular machine. A key rearrangement of the parts of this machine is called 'accommodation'. Here, transfer RNAs (tRNAs) carrying protein building blocks (amino acids) move into the ribosome. We identified a new functional region of the ribosome ('the accommodation corridor') and predicted that certain parts of this corridor are important for ribosome function. Our predictions were recently validated in studies by three experimental groups. In an additional separate set of studies that combined our simulations with single molecule experiments, a new picture of ribosome function has emerged. Rather than the ribosome machine parts moving in lock-step, both simulations and single molecule experiments show the tRNAs making large-scale reversible excursions in a trial-and-error fashion. This picture is consistent with a dynamic energy landscape view of the ribosome. The recent advent of the direct electron detector camera for use in cryo electron microscopy single particle reconstructions of ribosome structures has produced an avalanche of high resolution structures of ribosomes rivaling X-ray crystallography. We are using the methods developed in our molecular simulations of the ribosome to produce automated high resolution fits of this new and exciting data. [Preview Abstract] |
Saturday, October 17, 2015 1:36PM - 1:48PM |
K9.00002: Investigation of coherence in light harvesting proteins from cyanobacteria and cryptophytes with Free electron laser Raimund Fromme Photosynthesis plays a crucial role in supporting life on Earth and regulating CO$_{2}$ levels. Therefore, comprehensive understanding of light absorption processes from light harvesting proteins involved in photosynthesis is of the greatest importance for mimicking these functions in human designed systems. In cyanobacteria, proteins of the phycobilisome, namely, phycocyanin (PC)$^{5}$ allophycocyanin (APC) and phycoerythrin(PE) harvest light and transfer the excitation energy to reaction centers where the charge separation takes place. The relatively new technique of serial femtosecond crystallography with free electron lasers (SFX) $^{1-4,\, 7-8}$ allows for the first time to study the process of absorption and excitation energy transfer in the time zone of hundreds of femtoseconds to 100 pico seconds correlated with high resolution structures. $^{9}$ The development of new techniques of protein crystal delivery allows the use of down to 0.1 mg protein to get complete structural data with a resolution of up to 1.75 A resolution. $^{10-11}$ [Preview Abstract] |
Saturday, October 17, 2015 1:48PM - 2:00PM |
K9.00003: Path Similarity Analysis: a Method for Quantifying Macromolecular Transition Pathways Sean Seyler, Avishek Kumar, Michael Thorpe, Oliver Beckstein We develop a \emph{Path Similarity Analysis} (PSA) approach to quantify the (dis)similarity of macromolecular transition paths, which are curves in a high-dimensional space. Quantitatively comparing these paths is necessary to, for instance, assess the performance of the varied enhanced path-sampling algorithms. Our approach can access the full information in $3N$-dimensional trajectories in configuration space and overcomes the limitations of low-dimensional projections and heuristic collective variables. We employ the Hausdorff or Fr\'echet metrics from computational geometry to measure a distance between piecewise-linear curves. Using the closed-to-open transition of the enzyme adenylate kinase (AdK) in its substrate-free form as a testbed, we compare a range of path-sampling algorithms, including the molecular dynamics (MD) approaches dynamic importance sampling (DIMS-MD) and targeted MD (TMD), geometrical targeting (FRODA), and elastic network-based methods. The new concept of a Hausdorff-pair map enabled us to extract the molecular structural determinants responsible for geometric differences in AdK transition paths, namely a set of conserved salt bridges whose charge-charge interactions are fully modeled in DIMS-MD but not in FRODA. [Preview Abstract] |
Saturday, October 17, 2015 2:00PM - 2:12PM |
K9.00004: Partial Unfolding and Refolding for Structure Refinement: A Unified Approach of Geometric Simulations and Molecular Dynamics Paul Campitelli, Avishek Kumar, Banu Ozkan, Michael Thorpe The most successful protein structure prediction methods to date have been template-based modeling (TBM) or homology modeling, which predicts protein structure based on experimental structures. These high accuracy predictions sometimes retain structural errors due to incorrect templates or a lack of accurate templates in the case of low sequence similarity, making these structures inadequate in drug-design studies or molecular dynamics simulations. We have developed a new physics based approach to the protein refinement problem by mimicking the mechanism of chaperons that rehabilitate misfolded proteins. The template structure is unfolded by selectively (targeted) pulling on different portions of the protein using the geometric based technique FRODA, and then refolded using hierarchically restrained replica exchange molecular dynamics simulations (hr-REMD). [Preview Abstract] |
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