Enzymes play a pivotal role in various industries by enabling efficient, eco-friendly, and sustainable chemical processes. However, the low turnover rates and poor substrate selectivity of enzymes ...limit their large-scale applications. Rational computational enzyme design, facilitated by computational algorithms, offers a more targeted and less labor-intensive approach. There has been notable advancement in employing rational computational protein engineering strategies to overcome these issues, it has not been comprehensively reviewed so far. This article reviews recent developments in rational computational enzyme design, categorizing them into three types: structure-based, sequence-based, and data-driven machine learning computational design. Case studies are presented to demonstrate successful enhancements in catalytic activity, stability, and substrate selectivity. Lastly, the article provides a thorough analysis of these approaches, highlights existing challenges and potential solutions, and offers insights into future development directions.
The computational fabrication community is developing an increasing interest in the use of patterned surfaces, which can be designed to show ornamental and unconventional aesthetics or to perform as ...a proper structural material with a wide range of features. Geometrically designing and controlling the deformation capabilities of these patterns in response to external stimuli is a complex task due to the large number of variables involved. This paper introduces a method for generating sets of tileable and exchangeable flat patterns as well as a model-reduction strategy that enables their mechanical simulation at interactive rates. This method is included in a design pipeline that aims to turn any general flat surface into a pattern tessellation, which is able to deform under a given loading scenario. To validate our approach, we apply it to different contexts, including real-scale 3D printed specimens, for which we compare our results with the ones provided by a ground-truth solver.
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•Patterns are interesting from a visual and a mechanical perspective.•Their computational design is complex and an intriguing task.•We provide an efficient simulation model with our generated flat patterns.•Pipeline for direct design of tiled patterns’ assemblies.•Design exploration with an interactive tool that manages geometry and loads.
This paper addresses the design of surface shells as assemblies of tileable, flat geometric patterns with predictable performance in response to mechanical stimuli. We design a family of tileable and ...fabricable patterns represented as triangle meshes, which can be assembled for creating surface tessellations. First, a regular recursive subdivision of the planar space generates different geometric configurations for candidate patterns, having interesting and varied aesthetic properties. Then, a refinement step addresses manufacturability by solving for non-manifold configurations and sharp angles that would produce disconnected or weak patterns. We devise a strategy for creating continuous variations on the geometry of individual patterns, in both aesthetics and behavior, to enrich the catalog of available designs. Finally, we simulate our patterns to evaluate their mechanical response when loaded in different scenarios targeting out-of-plane bending. Through a simple browsing interface, we show that our patterns span a variety of different bending behaviors. The result is a catalog of patterns with varied aesthetics and predefined mechanical behavior, to use for the direct design of mechanical metamaterials. To assess the feasibility of our design-to-fabricate approach, we show fabricated 3D objects with different curvatures, and compare physical and simulated experiments.
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•Tileable geometric patterns, generated through recursive subdivision and refinement for manufacturability.•The patterns exhibit diverse mechanical behaviors computed in standard out-of-plane bending scenarios.•Strategy for domain augmentation by variating continuous parameters.•Navigation of a design catalog to select desirable aesthetic and mechanical qualities.•Design-to-fabricate approach validated through digital fabrication of 3D objects in comparison with simulations.
In this study, the first nanomaterial-supported molecularly imprinted polymer (MIP)-based electrochemical approach was proposed to achieve the successful detection of cefdinir (CFD). Here, p-amino ...benzoic acid (p-ABA) was used as the monomer and the photopolymerization method was chosen to form MIP on a glassy carbon electrode (GCE). ZnO nanoparticles (ZnO NPs) were added to the MIP sensor to increase sensitivity and create high porosity. Through the use of cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), characterization investigations confirmed the alterations at each stage of the MIP production process. Electrochemical (cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS)) and scanning electron microscopy (SEM) methods were used for study the characterization studies of the MIP-based nanocomposite sensor. The measurement of MIP parameters, such as the addition of nanoparticles, the removal procedure, the rebinding period, the monomer ratio, etc., was done using the differential pulse voltammetry (DPV). The findings showed that when ZnO NPs were added, the signal was three times higher than when MIPs were used alone. Under the optimized conditions, CFD/4-ABA@ZnONPs/MIP/GCE showed a linear response in the concentration range between 7.5 pM and 100 pM with LOD and LOQ values of 2.06 pM and 6.86 pM, respectively. Anions, cations, and substances including uric acid, ascorbic acid, paracetamol, and dopamine were all used in the selectivity test. In addition, the imprinting factor (IF) study was carried out using compounds such as cefuroxime, cefazolin, cefixime, ceftazidime, and ceftriaxone, which have structural similarities with CFD, as well as impurities such as thiazolylacetyl glycine oxime (IMP-A), thiazolylacetyl glycine oxime acetal (IMP-B), and cefdinir lactone (IMP-E). The results showed that the proposed sensor was selective for CFD, as evidenced by the relative IF values of these impurities. The recovery studies of CFD were successfully applied to tablet dosage form samples, and the developed sensor demonstrated significant sensitivity and selectivity for rapid detection of CFD in tablet dosage form.
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•Designing MIP-based sensors using the PP technique.•Highly selective application in tablet dosage form samples.•The nanomaterial-assisted MIP sensor was applied to the tablet dosage form.•The sensor indicates detection range from 7.5 pM to 100 pM with a LOD of 2.06 pM.•Comprehensive assessment of sensor accuracy by computational design.
We present a computational method for interactive 3D design and rationalization of surfaces via
auxetic
materials, i.e., flat flexible material that can stretch uniformly up to a certain extent. A ...key motivation for studying such material is that one can approximate doubly-curved surfaces (such as the sphere) using only flat pieces, making it attractive for fabrication. We physically realize surfaces by introducing cuts into approximately inextensible material such as sheet metal, plastic, or leather. The cutting pattern is modeled as a regular triangular linkage that yields hexagonal openings of spatially-varying radius when stretched. In the same way that isometry is fundamental to modeling developable surfaces, we leverage
conformal
geometry to understand auxetic design. In particular, we compute a global conformal map with bounded scale factor to initialize an otherwise intractable non-linear optimization. We demonstrate that this global approach can handle non-trivial topology and non-local dependencies inherent in auxetic material. Design studies and physical prototypes are used to illustrate a wide range of possible applications.
Computation-based approaches in design have emerged in the last decades and rapidly became popular among architects and other designers. Design professionals and researchers adopted different ...terminologies to address these approaches. However, some terms are used ambiguously and inconsistently, and different terms are commonly used to express the same concept. This paper discusses computational design (CD) and proposes an improved and sound taxonomy for a set of key CD terms, namely, parametric, generative, and algorithmic design, based on an extensive literature review from which different definitions by various authors were collected, analyzed, and compared.
The rise of antibiotic resistance calls for new therapeutics targeting resistance factors such as the New Delhi metallo-β-lactamase 1 (NDM-1), a bacterial enzyme that degrades β-lactam antibiotics. ...We present structure-guided computational methods for designing peptide macrocycles built from mixtures of l- and d-amino acids that are able to bind to and inhibit targets of therapeutic interest. Our methods explicitly consider the propensity of a peptide to favor a binding-competent conformation, which we found to predict rank order of experimentally observed IC
values across seven designed NDM-1- inhibiting peptides. We were able to determine X-ray crystal structures of three of the designed inhibitors in complex with NDM-1, and in all three the conformation of the peptide is very close to the computationally designed model. In two of the three structures, the binding mode with NDM-1 is also very similar to the design model, while in the third, we observed an alternative binding mode likely arising from internal symmetry in the shape of the design combined with flexibility of the target. Although challenges remain in robustly predicting target backbone changes, binding mode, and the effects of mutations on binding affinity, our methods for designing ordered, binding-competent macrocycles should have broad applicability to a wide range of therapeutic targets.
This paper discusses the foundations of a bio-based material paradigm for architecture. It argues that moving from a current reliance on the non-renewable materials of the geosphere, to the renewable ...and fundamentally cyclical materials of the biosphere can establish alternate foundations for thinking alternative sustainable building practices. By positioning architecture and the built environment as a particular case for bio-based materials, where the longer life spans of buildings support better carbon storage, this paper identifies the bottlenecks that limit their adaptation into the way architecture is thought, designed and built. If architectural ideation and design is traditionally understood through the durable and the permanent, our aim here is to challenge this foundation and bring forth the fundamental differences that bio-based materials engender. With focus on the embedded lifespans of living materials, the fundamental circularity and degradability of biomass and resulting transformative life cycles of the artefacts that they embody, this paper asks how a new representational framework for bio-based material paradigm can be conceptualised, instrumentalised and in turn materialised. The paper supports this positioning through a presentation of a series of methodological probes. The probes outline strategies for new methodologies by which we can capture, predict and steer the transformations of living materials and functionalise them as part of an architectural performance.
Curves play a fundamental role across computer graphics, physical simulation, and mathematical visualization, yet most tools for curve design do nothing to prevent crossings or self-intersections. ...This article develops efficient algorithms for (self-)repulsion of plane and space curves that are well-suited to problems in computational design. Our starting point is the so-called
tangent-point energy
, which provides an infinite barrier to self-intersection. In contrast to local collision detection strategies used in, e.g., physical simulation, this energy considers interactions between all pairs of points, and is hence useful for global shape optimization: local minima tend to be aesthetically pleasing, physically valid, and nicely distributed in space. A reformulation of gradient descent based on a
Sobolev-Slobodeckij inner product
enables us to make rapid progress toward local minima—independent of curve resolution. We also develop a hierarchical multigrid scheme that significantly reduces the per-step cost of optimization. The energy is easily integrated with a variety of constraints and penalties (e.g., inextensibility, or obstacle avoidance), which we use for applications including curve packing, knot untangling, graph embedding, non-crossing spline interpolation, flow visualization, and robotic path planning.
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