Using Structural Bioinformatics to Model and Design Membrane Proteins

Cells require membrane proteins for a wide spectrum of critical functions. Transmembrane proteins enable cells to communicate with its environment, catalysis, ion transport and scaffolding. The functional roles of membrane proteins are specified by their sequence composition and precise three dimensional folding. The exact mechanisms driving folding of membrane proteins is still not fully understood. Further, the association between membrane proteins occurs with pinpoint specificity. For example, there exists common sequence features within families of transmembrane receptors, yet there is little cross talk between families. Therefore, we ask how membrane proteins dial in their specificity and what factors are responsible for adoption of native structure. Advancements in membrane protein structure determination methods has been followed by a sharp increase in three dimensional structures. Structural bioinfomatics has been utilized effectively to study water soluble proteins. The field is now entering an era where structural bioinformatics can be applied to modeling membrane proteins without structure and engineering novel membrane proteins. The transmembrane domains of membrane proteins were first categorized structurally. From this analysis, we are able to describe the ways in which membrane proteins fold and associate. We further derived sequence profiles for the commonly occurring structural motifs, enabling us to investigate the role of amino acids within the bilayer. Utilizing these tools, a transmembrane structural model was constructed of principle cell surface receptors (integrins). The structural model enabled understanding of possible mechanisms used to signal and to propose a novel membrane protein packing motif. In addition, novel scoring functions for membrane proteins were developed and applied to modeling membrane proteins. We derived the first all-atom membrane statistical potential and introduced the usage of exposed volume. These potentials allowed modeling of complex interactions in membrane proteins, such as salt bridges. To understand the geometric preferences of salt bridges, we surveyed a structural database. We learned about large biases in salt bridge orientations that will be useful in modeling and design. Lastly, we combine these structural bioinformatic efforts, enabling us to model membrane proteins in ways which were previously inaccessible

The Grizzly, April 18, 1986

The Bomb is Dropped; Policy Could Can Kegs • Admissions Video to Draw High School Seniors • CAB Spring Weekend Twists Around the Corner! • Administration\u27s Letter: Clearing Up the Cloudy Water • Get Your Ruby • Proposed Alcohol Regulations • Political Science\u27s Fitzpatrick to Focus on Constitution • Richter Joins Pavarotti • Greek Week Results • College Republicans Meet in Harrisburg • Perreten in Select Group to Interpret Humanities • Novack to Study Technology\u27s Effects on French Life • Lift-A-Thon: Pressing Weights for Progress • Women\u27s LAX Takes Two • Linksters Drive to 7-1 Record • Men\u27s LAX Strong at 5-2 • Rowson a Threat for Gold in Five Events • A Sterling Suggestion! Brown to be Tattooed • O\u27Toole Hurdles School Record • Men\u27s Tennis • Bears Battle Back • Hadler\u27s Medical Serieshttps://digitalcommons.ursinus.edu/grizzlynews/1988/thumbnail.jp

The James Webb Space Telescope Mission: Optical Telescope Element Design, Development, and Performance

The James Webb Space Telescope (JWST) is a large, infrared space telescope that has recently started its science program which will enable breakthroughs in astrophysics and planetary science. Notably, JWST will provide the very first observations of the earliest luminous objects in the Universe and start a new era of exoplanet atmospheric characterization. This transformative science is enabled by a 6.6 m telescope that is passively cooled with a 5-layer sunshield. The primary mirror is comprised of 18 controllable, low areal density hexagonal segments, that were aligned and phased relative to each other in orbit using innovative image-based wavefront sensing and control algorithms. This revolutionary telescope took more than two decades to develop with a widely distributed team across engineering disciplines. We present an overview of the telescope requirements, architecture, development, superb on-orbit performance, and lessons learned. JWST successfully demonstrates a segmented aperture space telescope and establishes a path to building even larger space telescopes.Comment: accepted by PASP for JWST Overview Special Issue; 34 pages, 25 figure

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

State Modeling and Pass Automation in Spacecraft Control

International Telemetering Conference Proceedings / October 28-31, 1996 / Town and Country Hotel and Convention Center, San Diego, CaliforniaThe Integrated Monitoring and Control COTS System (IMACCS) was developed as a proof-of-concept to show that commercial off-the-shelf (COTS) products could be integrated to provide spacecraft ground support faster and cheaper than current practices. A key component of IMACCS is the Altair Mission Control System (AMCS), one of several commercial packages available for satellite command and control. It is distinguished from otherwise similar tools by its implementation of Finite State Modeling as part of its expert system capability. Using the Finite State Modeling and State Transition capabilities of the ALTAIR Mission Control System (AMCS), IMACCS was enhanced to provide automated monitoring, routine pass support, anomaly resolution, and emergency "lights on again" response. Orbit determination and production of typical flight dynamics products, such as acquisition times and vectors, have also been automated.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection

Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers

Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection after vaccination have not been established. Here, we selected groups of 6 rhesus macaques with either high or low serum nAb titers from a total of 78 animals immunized with recombinant native-like (SOSIP) Env trimers. Repeat intrarectal challenge with homologous tier 2 SHIVBG505 led to rapid infection in unimmunized and low-titer animals. High-titer animals, however, demonstrated protection that was gradually lost as nAb titers waned over time. An autologous serum ID50 nAb titer of ∼1:500 afforded more than 90% protection from medium-dose SHIV infection. In contrast, antibody-dependent cellular cytotoxicity and T cell activity did not correlate with protection. Therefore, Env protein-based vaccination strategies can protect against hard-to-neutralize SHIV challenge in rhesus macaques by inducing tier 2 nAbs, provided appropriate neutralizing titers can be reached and maintained