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At least 847 records · Page 47

The Problem of Size in Robust Design

To facilitate the effective solution of multidisciplinary, multiobjective complex design problems, a departure from the traditional parametric design analysis and single objective optimization approaches is necessary in the preliminary stages of design. A necessary tradeoff becomes one of efficiency vs. accuracy as approximate models are sought to allow fast analysis and effective exploration of a preliminary design space. In this paper we apply a general robust design approach for efficient and comprehensive preliminary design to a large complex system: a high speed civil transport (HSCT) aircraft. Specifically, we investigate the HSCT wing configuration design, incorporating life cycle economic uncertainties to identify economically robust solutions. The approach is built on the foundation of statistical experimentation and modeling techniques and robust design principles, and is specialized through incorporation of the compromise Decision Support Problem for multiobjective design. For large problems however, as in the HSCT example, this robust design approach developed for efficient and comprehensive design breaks down with the problem of size - combinatorial explosion in experimentation and model building with number of variables -and both efficiency and accuracy are sacrificed. Our focus in this paper is on identifying and discussing the implications and open issues associated with the problem of size for the preliminary design of large complex systems.

Koch, Patrick N.↗

Reinventing The Design Process: Teams and Models

The future of space mission designing will be dramatically different from the past. Formerly, performance-driven paradigms emphasized data return with cost and schedule being secondary issues. Now and in the future, costs are capped and schedules fixed-these two variables must be treated as independent in the design process. Accordingly, JPL has redesigned its design process. At the conceptual level, design times have been reduced by properly defining the required design depth, improving the linkages between tools, and managing team dynamics. In implementation-phase design, system requirements will be held in crosscutting models, linked to subsystem design tools through a central database that captures the design and supplies needed configuration management and control. Mission goals will then be captured in timelining software that drives the models, testing their capability to execute the goals. Metrics are used to measure and control both processes and to ensure that design parameters converge through the design process within schedule constraints. This methodology manages margins controlled by acceptable risk levels. Thus, teams can evolve risk tolerance (and cost) as they would any engineering parameter. This new approach allows more design freedom for a longer time, which tends to encourage revolutionary and unexpected improvements in design.

Wall, Stephen D.↗

Multi-Disciplinary Design Optimization Using WAVE

The current preliminary design tools lack the product performance, quality and cost prediction fidelity required to design Six Sigma products. They are also frequently incompatible with the tools used in detailed design, leading to a great deal of rework and lost or discarded data in the transition from preliminary to detailed design. Thus, enhanced preliminary design tools are needed in order to produce adequate financial returns to the business. To achieve this goal, GEAE has focused on building the preliminary design system around the same geometric 3D solid model that will be used in detailed design. With this approach, the preliminary designer will no longer convert a flowpath sketch into an engine cross section but rather, automatically create 3D solid geometry for structural integrity, life, weight, cost, complexity, producibility, and maintainability assessments. Likewise, both the preliminary design and the detailed design can benefit from the use of the same preliminary part sizing routines. The design analysis tools will also be integrated with the 3D solid model to eliminate manual transfer of data between programs. GEAE has aggressively pursued the computerized control of engineering knowledge for many years. Through its study and validation of 3D CAD programs and processes, GEAE concluded that total system control was not feasible at that time. Prior CAD tools focused exclusively on detail part geometry and Knowledge Based Engineering systems concentrated on rules input and data output. A system was needed to bridge the gap between the two to capture the total system. With the introduction of WAVE Engineering from UGS, the possibilities of an engineering system control device began to formulate. GEAE decided to investigate the new WAVE functionality to accomplish this task. NASA joined GEAE in funding this validation project through Task Order No. 1. With the validation project complete, the second phase under Task Order No. 2 was established to develop an associative control structure (framework) in the UG WAVE environment enabling multi-disciplinary design of turbine propulsion systems. The capabilities of WAVE were evaluated to assess its use as a rapid optimization and productivity tool. This project also identified future WAVE product enhancements that will make the tool still more beneficial for product development.

Irwin, Keith↗

Launch Vehicle Design Process: Characterization, Technical Integration, and Lessons Learned

Engineering design is a challenging activity for any product. Since launch vehicles are highly complex and interconnected and have extreme energy densities, their design represents a challenge of the highest order. The purpose of this document is to delineate and clarify the design process associated with the launch vehicle for space flight transportation. The goal is to define and characterize a baseline for the space transportation design process. This baseline can be used as a basis for improving effectiveness and efficiency of the design process. The baseline characterization is achieved via compartmentalization and technical integration of subsystems, design functions, and discipline functions. First, a global design process overview is provided in order to show responsibility, interactions, and connectivity of overall aspects of the design process. Then design essentials are delineated in order to emphasize necessary features of the design process that are sometimes overlooked. Finally the design process characterization is presented. This is accomplished by considering project technical framework, technical integration, process description (technical integration model, subsystem tree, design/discipline planes, decision gates, and tasks), and the design sequence. Also included in the document are a snapshot relating to process improvements, illustrations of the process, a survey of recommendations from experienced practitioners in aerospace, lessons learned, references, and a bibliography.

Blair, J. C.↗

Geometry Modeling and Grid Generation for Design and Optimization

Geometry modeling and grid generation (GMGG) have played and will continue to play an important role in computational aerosciences. During the past two decades, tremendous progress has occurred in GMGG; however, GMGG is still the biggest bottleneck to routine applications for complicated Computational Fluid Dynamics (CFD) and Computational Structures Mechanics (CSM) models for analysis, design, and optimization. We are still far from incorporating GMGG tools in a design and optimization environment for complicated configurations. It is still a challenging task to parameterize an existing model in today's Computer-Aided Design (CAD) systems, and the models created are not always good enough for automatic grid generation tools. Designers may believe their models are complete and accurate, but unseen imperfections (e.g., gaps, unwanted wiggles, free edges, slivers, and transition cracks) often cause problems in gridding for CSM and CFD. Despite many advances in grid generation, the process is still the most labor-intensive and time-consuming part of the computational aerosciences for analysis, design, and optimization. In an ideal design environment, a design engineer would use a parametric model to evaluate alternative designs effortlessly and optimize an existing design for a new set of design objectives and constraints. For this ideal environment to be realized, the GMGG tools must have the following characteristics: (1) be automated, (2) provide consistent geometry across all disciplines, (3) be parametric, and (4) provide sensitivity derivatives. This paper will review the status of GMGG for analysis, design, and optimization processes, and it will focus on some emerging ideas that will advance the GMGG toward the ideal design environment.

Samareh, Jamshid A.↗

Designing Domain-Specific HUMS Architectures: An Automated Approach

The HUMS automation system automates the design of HUMS architectures. The automated design process involves selection of solutions from a large space of designs as well as pure synthesis of designs. Hence the whole objective is to efficiently search for or synthesize designs or parts of designs in the database and to integrate them to form the entire system design. The automation system adopts two approaches in order to produce the designs: (a) Bottom-up approach and (b) Top down approach. Both the approaches are endowed with a Suite of quantitative and quantitative techniques that enable a) the selection of matching component instances, b) the determination of design parameters, c) the evaluation of candidate designs at component-level and at system-level, d) the performance of cost-benefit analyses, e) the performance of trade-off analyses, etc. In short, the automation system attempts to capitalize on the knowledge developed from years of experience in engineering, system design and operation of the HUMS systems in order to economically produce the most optimal and domain-specific designs.

Mukkamala, Ravi↗

Holistic Design for Total Product Well Being

Recent hardware development work at NASA's Marshall Space Flight Center creates and argument for the use of a holistic design approach as opposed to a piece part design approach. A piece part design approach being one where individual pieces are developed to their finished state having to meet certain interface and human engineering requirements without much consideration to the final product as a whole. A holistic design approach being one where the final product is evaluated early and frequently during the design process, and individual parts are developed with consideration to how they interact a whole,and how they interact with the user and environment. Examples from the development of the Materials Science Research Rack - 1 will illustrate: a design failure due to piece part design; a design save, due to a failure of piece part design, but saved by evaluating the design holistically; and a design success due to a holistic design approach.

Adams, Chris W.↗

Aerospace Power Systems Design and Analysis (APSDA) Tool

The conceptual design of space and/or planetary electrical power systems has required considerable effort. Traditionally, in the early stages of the design cycle (conceptual design), the researchers have had to thoroughly study and analyze tradeoffs between system components, hardware architectures, and operating parameters (such as frequencies) to optimize system mass, efficiency, reliability, and cost. This process could take anywhere from several months to several years (as for the former Space Station Freedom), depending on the scale of the system. Although there are many sophisticated commercial software design tools for personal computers (PC's), none of them can support or provide total system design. To meet this need, researchers at the NASA Lewis Research Center cooperated with Professor George Kusic from the University of Pittsburgh to develop a new tool to help project managers and design engineers choose the best system parameters as quickly as possible in the early design stages (in days instead of months). It is called the Aerospace Power Systems Design and Analysis (APSDA) Tool. By using this tool, users can obtain desirable system design and operating parameters such as system weight, electrical distribution efficiency, bus power, and electrical load schedule. With APSDA, a large-scale specific power system was designed in a matter of days. It is an excellent tool to help designers make tradeoffs between system components, hardware architectures, and operation parameters in the early stages of the design cycle. user interface. It operates on any PC running the MS-DOS (Microsoft Corp.) operating system, version 5.0 or later. A color monitor (EGA or VGA) and two-button mouse are required. The APSDA tool was presented at the 30th Intersociety Energy Conversion Engineering Conference (IECEC) and is being beta tested at several NASA centers. Beta test packages are available for evaluation by contacting the author.

Truong, Long V.↗

Generative Representations for Computer-Automated Evolutionary Design

With the increasing computational power of computers, software design systems are progressing from being tools for architects and designers to express their ideas to tools capable of creating designs under human guidance. One of the main limitations for these computer-automated design systems is the representation with which they encode designs. If the representation cannot encode a certain design, then the design system cannot produce it. To be able to produce new types of designs, and not just optimize pre-defined parameterizations, evolutionary design systems must use generative representations. Generative representations are assembly procedures, or algorithms, for constructing a design thereby allowing for truly novel design solutions to be encoded. In addition, by enabling modularity, regularity and hierarchy, the level of sophistication that can be evolved is increased. We demonstrate the advantages of generative representations on two different design domains: the evolution of spacecraft antennas and the evolution of 3D objects.

Hornby, Gregory S.↗

Cross Cutting Structural Design for Exploration Systems

The challenge of our new National Space Policy and NASA's Vision for Space Exploration (VSE) is keyed to the development of more effective space access and transportation systems. Optimizing in-space systems through innovative cross cutting structural designs that reduce mass, combine functional requirements and improve performance can significantly advance spacecraft designs to meet the ever growing demands of our new National Space Policy. Dependence on limited structural designs is no longer an option. We must create robust materials, forms, function and evolvable systems. We must advance national policy objectives in the design, development, test and operation of multi-billion dollar new generation crew capsules by enabling them to evolve in meeting the requirements of long duration missions to the moon and mars. This paper discusses several current issues and major design drivers for consideration in structural design of advanced spacecraft systems. Approaches to addressing these multifunctional requirements is presented as well as a discussion on utilizing Functional Analysis System Technique (FAST) in developing cross cutting structural designs for future spacecraft. It will be shown how easy it is to deploy such techniques in any conceptual architecture definition or ongoing preliminary design. As experts in merging mission, safety and life support requirements of the frail human existence into robust vehicle and habitat design, we will conquer the final frontier, harness new resources and develop life giving technologies for mankind through more innovative designs. The rocket equation tells us that a reduction in mass optimizes our propulsive results. Primary and secondary structural elements provide for the containment of gases, fluids and solids; translate and sustain loads/impacts; conduct/radiate thermal energy; shield from the harmful effects of radiation; provide for grounding/bonding of electrical power systems; compartmentalize operational functions; and provide physical interface with multiple systems. How can we redefine, combine, substitute, rearrange and otherwise modify our structural systems to reduce mass? New technologies will be needed to fill knowledge gaps and propagate new design methods. Such an integrated process is paramount in maintaining U.S. leadership and in executing our national policy goals. The cross cutting process can take many forms, but all forms will have a positive affect on the demanding design environment through initial radical thinking. The author will illustrate such cross cutting results achievable through a formal process called FAST. The FAST example will be used to show how a multifunctional structural system concept for long duration spacecraft might be generated.

Semmes, Edmund B.↗

Designing for Our Future in Space

Over the past several years, the disciplines of architecture and human factors have been increasingly recognized as specialties that have focused upon "human-centered design" in the development of spacecraft and surface habitats. These specialties have been instrumental in the conceptual design of overall spacecraft configurations and layouts, as well as habitability outfitting hardware, such as the galley, hygiene facility, sleep quarters, or the layout of displays and controls. From the human-centered perspective, this approach to design assists in the mitigation of risk when designing for an extreme environment such as space. It takes into account the human s physical and cognitive capabilities and limitations, the human s performance in the context of human space flight, the human s interaction with machines that are both physically and cognitively complex, the activities required of the human to accomplish the goals of missions, and the use of design practices that promote products to enable human activity. It is this latter aspect - the use of design practices that promote products to enable human activity - that is the focus of the approach used by the Rhode Island School of Design (RISD) in collaboration with the Habitability and Human Factors Branch (HHFB) at the NASA Johnson Space Center (JSC). During the past few years, there has been a growing recognition of the value added by utilizing industrial designers to further the conceptual development of space hardware, that when used in conjunction with architecture and human factors, provides a robust solution to the design challenge. The "Design for Extreme Environments" Studio at RISD has taken suggested design topics from the NASA JSC HHFB and asked the students to investigate solutions to these challenges. The topics have demanded that the student pay particular attention to a variety of aspects of the space environment and understand how the human responds to each. The student must then adapt the design to these responses. The studio environment has been one way to introduce these challenges, but providing for an "in-residence" opportunity at JSC has given the students a broader vision and set of experiences. The accompanying presentation highlights the studio as well as in-residence work that has been accomplished.

Connolly, Janis↗

Interactive Inverse Design Optimization of Fuselage Shape for Low-Boom Supersonic Concepts

This paper introduces a tool called BOSS (Boom Optimization using Smoothest Shape modifications). BOSS utilizes interactive inverse design optimization to develop a fuselage shape that yields a low-boom aircraft configuration. A fundamental reason for developing BOSS is the need to generate feasible low-boom conceptual designs that are appropriate for further refinement using computational fluid dynamics (CFD) based preliminary design methods. BOSS was not developed to provide a numerical solution to the inverse design problem. Instead, BOSS was intended to help designers find the right configuration among an infinite number of possible configurations that are equally good using any numerical figure of merit. BOSS uses the smoothest shape modification strategy for modifying the fuselage radius distribution at 100 or more longitudinal locations to find a smooth fuselage shape that reduces the discrepancies between the design and target equivalent area distributions over any specified range of effective distance. For any given supersonic concept (with wing, fuselage, nacelles, tails, and/or canards), a designer can examine the differences between the design and target equivalent areas, decide which part of the design equivalent area curve needs to be modified, choose a desirable rate for the reduction of the discrepancies over the specified range, and select a parameter for smoothness control of the fuselage shape. BOSS will then generate a fuselage shape based on the designer's inputs in a matter of seconds. Using BOSS, within a few hours, a designer can either generate a realistic fuselage shape that yields a supersonic configuration with a low-boom ground signature or quickly eliminate any configuration that cannot achieve low-boom characteristics with fuselage shaping alone. A conceptual design case study is documented to demonstrate how BOSS can be used to develop a low-boom supersonic concept from a low-drag supersonic concept. The paper also contains a study on how perturbations in the equivalent area distribution affect the ground signature shape and how new target area distributions for low-boom signatures can be constructed using superposition of equivalent area distributions derived from the Seebass-George-Darden (SGD) theory.

Li, Wu↗

Application of a Modified Universal Design Survey for Evaluation of Ares 1 Ground Crew Worksites

Operability is a driving requirement for NASA's Ares 1 launch vehicle. Launch site ground operations include several operator tasks to prepare the vehicle for launch or to perform maintenance. Ensuring that components requiring operator interaction at the launch site are designed for optimal human use is a high priority for operability. To support design evaluation, the Ares 1 Upper Stage (US) element Human Factors Engineering (HFE) group developed a survey based on the Universal Design approach. Universal Design is a process to create products that can be used effectively by as many people as possible. Universal Design per se is not a priority for Ares 1 because launch vehicle processing is a specialized skill and not akin to a consumer product that should be used by all people of all abilities. However, applying principles of Universal Design will increase the probability of an error free and efficient design which is a priority for Ares 1. The Design Quality Evaluation Survey centers on the following seven principles: (1) Equitable use, (2) Flexibility in use, (3) Simple and intuitive use, (4) Perceptible information, (5) Tolerance for error, (6) Low physical effort, (7) Size and space for approach and use. Each principle is associated with multiple evaluation criteria which were rated with the degree to which the statement is true. All statements are phrased in the utmost positive, or the design goal so that the degree to which judgments tend toward "completely agree" directly reflects the degree to which the design is good. The Design Quality Evaluation Survey was employed for several US analyses. The tool was found to be most useful for comparative judgments as opposed to an assessment of a single design option. It provided a useful piece of additional data when assessing possible operator interfaces or worksites for operability

Blume, Jennifer L.↗

Advancing the State-of-the-Practice for Liquid Rocket Engine Injector Design

Current shortcomings in both the overall injector design process and its underlying combustion stability assessment methodology are rooted in the use of empirically based or low fidelity representations of complex physical phenomena and geometry details that have first order effects on performance, thermal environments and combustion stability. The result is a design and analysis capability that is often inadequate to reliably arrive at a suitable injector design in an efficient manner. Specifically, combustion instability has been particularly difficult to predict and mitigate. Large hydrocarbon-fueled booster engines have been especially problematic in this regard. Where combustion instability has been a problem, costly and time-consuming redesign efforts have often been an unfortunate consequence. This paper presents an overview of a recently completed effort at NASA Marshall Space Flight Center to advance the state-of-the-practice for liquid rocket engine injector design. Multiple perturbations of a gas-centered swirl coaxial (GCSC) element that burned gaseous oxygen and RP-1 were designed, assessed for combustion stability, and tested. Three designs, one stable, one marginally unstable and one unstable, were used to demonstrate both an enhanced overall injector design process and an improved combustion stability assessment process. High-fidelity results from state-of-the-art computational fluid dynamics CFD simulations were used to substantially augment and improve the injector design methodology. The CFD results were used to inform and guide the overall injector design process. They were also used to upgrade selected empirical or low-dimensional quantities in the ROCket Combustor Interactive Design (ROCCID) stability assessment tool. Hot fire single element injector testing was used to verify both the overall injector designs and the stability assessments. Testing was conducted at the Air Force Research Laboratory and at Purdue University. Companion papers provide details of the overall injector design process, full- and sub-scale testing, ROCCID-based stability assessments and the CFD simulations.

Tucker, P. K.↗

Buckling Design and Imperfection Sensitivity of Sandwich Composite Launch-Vehicle Shell Structures

Composite materials are increasingly being considered and used for launch-vehicle structures. For shell structures, such as interstages, skirts, and shrouds, honeycomb-core sandwich composites are often selected for their structural efficiency. Therefore, it is becoming increasingly important to understand the structural response, including buckling, of sandwich composite shell structures. Additionally, small geometric imperfections can significantly influence the buckling response, including considerably reducing the buckling load, of shell structures. Thus, both the response of the theoretically perfect structure and the buckling imperfection sensitivity must be considered during the design of such structures. To address the latter, empirically derived design factors, called buckling knockdown factors (KDFs), were developed by NASA in the 1960s to account for this buckling imperfection sensitivity during design. However, most of the test-article designs used in the development of these recommendations are not relevant to modern launch-vehicle constructions and material systems, and in particular, no composite test articles were considered. Herein, a two-part study on composite sandwich shells to (1) examine the relationship between the buckling knockdown factor and the areal mass of optimized designs, and (2) to interrogate the imperfection sensitivity of those optimized designs is presented. Four structures from recent NASA launch-vehicle development activities are considered. First, designs optimized for both strength and stability were generated for each of these structures using design optimization software and a range of buckling knockdown factors; it was found that the designed areal masses varied by between 6.1% and 19.6% over knockdown factors ranging from 0.6 to 0.9. Next, the buckling imperfection sensitivity of the optimized designs is explored using nonlinear finite-element analysis and the as-measured shape of a large-scale composite cylindrical shell. When compared with the current buckling design recommendations, the results suggest that the current recommendations are overly conservative and that the development of new recommendations could reduce the acreage areal mass of many composite sandwich shell designs by between 4% and 19%, depending on the structure.

Schultz, Marc R.↗

Electrical Cable Design for Urban Air Mobility Aircraft

Urban Air Mobility (UAM) describes a new type of aviation focused on efficient flight within urban areas for moving people and goods. There are many different configurations of UAM vehicles, but they generally use an electric motor driving a propeller or ducted fan powered by batteries or a hybrid electric power generation system. Transmission cables are used to move energy from the storage or generation system to the electric motors. Though terrestrial power transmission cables are well established technology, aviation applications bring a whole host of new design challenges that are not typical considerations in terrestrial applications. Aircraft power transmission cable designs must compromise between resistance-per-length, weight-per-length, volume constraints, and other essential qualities. In this paper we use a multidisciplinary design optimization to explore the sensitivity of these qualities to a representative tiltwing turboelectric UAM aircraft concept. This is performed by coupling propulsion and thermal models for a given mission criteria. Results presented indicate that decreasing cable weight at the expense of increasing cable volume or cooling demand is effective at minimizing maximum takeoff weight (MTO). These findings indicate that subsystem designers should update their modeling approach in order to contribute to system-level optimality for highly-coupled novel aircraft. Mobility (UAM) vehicles have the potential to change urban and intra-urban transport in new and interesting ways. In a series of two papers Johnson et al.1 and Silva et al.2 presented four reference vehicle configurations that could service different niches in the UAM aviation category. Of those, this paper focuses on the Vertical Take-off and Landing (VTOL) tiltwing configuration shown in Figure 1. This configuration uses a turboelectric power system, feeding power from a turbo-generator through a system of transmission cables to four motors spinning large propellers on the wings. Previous work on electric cable subsystems leaves much yet to be explored, especially in the realm of subsystem coupling. Several aircraft optimization studies1, 3, 4 only considered aircraft electrical cable weight and ignored thermal effects. Electric and hybrid-electric aircraft studies by Mueller et al.5 and Hoelzen et al.6 selected a cable material but did not investigate alternative materials. Advanced cable materials have been examined by a number of authors: Alvarenga7 examined carbon nanotube (CNT) conductors for low-power applications. De Groh8, 9 examined CNT conductors for motor winding applications. Behabtu et al.,10 and Zhao et al.11 examined CNT conductors for a general applications. There were some studies that examined the thermal effects of cables but they did not allow the cable material to change; El-Kady12 optimized ground-cable insulation and cooling subject constraints. Vratny13 selected cable material based on vehicle power demand, and required resulting cable heat to be dissipated by the Thermal Management System (TMS). None of these previous studies allowed for the selection of the cable material based on a system level optimization goal. Instead, they focused on sub-system optimality such as minimum weight, which comes at the expense of incurring additional costs for other subsystems. Dama14 selected overhead transmission line materials using a weighting function and thermal constraints. However, that work was not coupled with any aircraft subsystems like a TMS. The traditional aircraft design approach, which relies on assembling groups of optimal subsystems, breaks down when considering novel aircraft concepts like the tiltwing vehicle. In a large part, this is because novel concepts have a much higher degree of interaction or coupling between subsystems. For example, when a cable creates heat, this heat needs to be dissipated by the TMS, which needs power supplied by the turbine, and delivering the power creates more heat. The cable, the TMS, and the turbine are all coupled. A change to one subsystem will affect all the other subsystems, much to the consternation of subsystem design experts. Multidisciplinary optimization is the design approach that can address these challenges. However, to fully take advantage of this, we must change the way we think about subsystem design. Specifically, we must move away from point design, and focus on creating solution spaces. The work presented in this paper uses the multidisciplinary optimization approach with aircraft level models to study the system-level sensitivity of cable traits: weight-per-length and resistance-per-length. Additionally, we examined the effects of vehicle imposed volume constraints on these traits. This is useful for three purposes: (1) to demonstrate a framework that can perform a coupled analysis between the aircraft thermal and propulsion systems, (2) to provide a method by which future cable designs can be evaluated against each other given a system-level design goal, (3) to provide insight into what cable properties may be promising for future research. This last element is explored given the caveat that the models contained in this analysis do not represent high-fidelity systems. Thus, while we can demonstrate coupling in between systems, the exact system-level sensitivity to a given parameter may change if a subsystem model or the assumptions governing that model change. The organization of this paper is as follows, in Sec II we outline a method to combine the VTOL vehicle design and cable information in order to produce cables sensitivity studies. Results analysis and discussion are contained in Sec III. Conclusions are presented in Sec IV.

Aretskin-Hariton, Eliot D.↗

De novo design and Rosetta-based assessment of high-affinity antibody variable regions (Fv) against the SARS-CoV -2 spike receptor binding domain ( RBD )

The continued emergence of new SARS-CoV-2 variants has accentuated the growing need for fast and reliable methods for the design of potentially neutralizing antibodies (Abs) to counter immune evasion by the virus. Here, we report on the de novo computational design of high-affinity Ab variable regions (Fv) through the recombination of VDJ genes targeting the most solvent-exposed hACE2-binding residues of the SARS-CoV-2 spike receptor binding domain (RBD) protein using the software tool OptMAVEn-2.0. Subsequently, we carried out computational affinity maturation of the designed variable regions through amino acid substitutions for improved binding with the target epitope. Immunogenicity of designs was restricted by preferring designs that match sequences from a 9-mer library of “human Abs” based on a human string content score. We generated 106 different antibody designs and reported in detail on the top five that trade-off the greatest computational binding affinity for the RBD with human string content scores. We further describe computational evaluation of the top five designs produced by OptMAVEn-2.0 using a Rosetta-based approach. We used Rosetta SnugDock for local docking of the designs to evaluate their potential to bind the spike RBD and performed “forward folding” with DeepAb to assess their potential to fold into the designed structures. Ultimately, our results identified one designed Ab variable region, P1.D1, as a particularly promising candidate for experimental testing. This effort puts forth a computational workflow for the de novo design and evaluation of Abs that can quickly be adapted to target spike epitopes of emerging SARS-CoV-2 variants or other antigenic targets.

59 BASIC BIOLOGICAL SCIENCES↗

Multidisciplinary concurrent optimization framework for multi-phase building design process

Modern day building design projects require multidisciplinary expertise from architects and engineers across various phases of the design (conceptual, preliminary, and detailed) and construction processes. The Architecture Engineering and Construction (AEC) community has recently shifted gears toward leveraging design optimization techniques to make well-informed decisions in the design of buildings. However, most of the building design optimization efforts are either multidisciplinary optimization confined to just a specific design phase (conceptual/preliminary/detailed) or single disciplinary optimization (structural/thermal/daylighting/energy) spanning across multiple phases. Complexity in changing the optimization setup as the design progresses through subsequent phases, interoperability issues between modeling and physics-based analysis tools used at later stages, and the lack of an appropriate level of design detail to get meaningful results from these sophisticated analysis tools are few challenges that limit multi-phase multidisciplinary design optimization (MDO) in the AEC field. Here this paper proposes a computational building design platform leveraging concurrent engineering techniques such as interactive problem structuring, simulation-based optimization using meta models for energy and daylighting (machine learning based) and tradespace visualization. The proposed multi-phase concurrent MDO framework is demonstrated by using it to design and optimize a sample office building for energy and daylighting objectives across multiple phases. Furthermore, limitations of the proposed framework and future avenues of research are listed.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗