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Roya Zandi

Publications and source records attributed to Roya Zandi.

At least 19 recordsLinked to original sources

ToolGate: An Executable Acceptance Pipeline for Tool-Dependent Scientific Benchmark Construction

Scientific benchmarks are commonly built by domain experts who write tasks and cross-check one another's work, or who adapt existing material from textbooks, published papers, and online resources. These routes can produce strong evaluations, but they require substantial per-item labor. Language models can reduce this repeated work by proposing candidates quickly. The remaining problem is acceptance. We target scientific questions whose answers require computations with specialist software rather than unaided reasoning alone. A candidate is invalid if its script fails or returns a different answer, or trivial if a model answers it without the software. We present ToolGate, which treats every generated item as a proposal and keeps it only if three gates pass. First, an executable solution script must reproduce the proposed answer when run with the scientific software. Second, randomized no-tool screening rejects candidates that models can already solve from the prompt alone. Third, a tool-using agent must solve each survivor within a fixed time limit. We instantiate ToolGate in FEniCSx with 500 generation attempts. The local-verification gate retains 478 candidates. For final reporting, we rescreen this pool after generation: two randomized no-tool screens exclude 222 from the reported pool, and direct GPT-5.5 API calls at medium reasoning (the API default) exclude another 121. Of the remaining 135, a GPT-5.5 Codex CLI agent with access to FEniCSx solves 130; exact deduplication leaves 128 unique protocol survivors. ToolGate turns repeated answer checking and difficulty screening into an auditable process while leaving domain design and final review to experts.

cs.AI

Learning Parameterized Nonlinear Elasticity on Curved Surfaces

We learn parameterized nonlinear elasticity on curved surfaces using a physics-informed neural network that enforces governing equations and boundary conditions directly through the loss function, enabling a single trained model to represent a continuous family of elastic equilibria across geometric and material parameters. Nonlinear elasticity on curved manifolds underlies the mechanics of crystalline shells, elastic membranes, and viral capsids, where curvature and topological defects determine equilibrium structure and stability. Traditional exact and finite element solvers rely on symmetry reduction and must be reinitialized for each parameter choice, limiting scalability when symmetry is broken or parameters vary. We validate the proposed learning-based solver on a benchmark problem from curved elasticity, namely the one-dimensional single disclination on a spheroidal surface with known exact and numerical solutions. The network accurately reproduces these solutions, including parameter combinations excluded from training, demonstrating generalization across geometry and material regimes. This study establishes a scalable framework for learning nonlinear elastic systems on curved manifolds and lays the groundwork for extensions to fully two-dimensional and multi-defect configurations relevant to protein shells and other curved elastic networks.

physics.bio-ph

Effects of Rim Fluctuations in Classical Nucleation Theory of Virus Capsids

Most spherical viruses exhibit icosahedral symmetry, yet the growth of viral shells remains poorly understood due to the short lifetimes and broad size distribution of assembly intermediates. Classical nucleation theory has been widely applied to describe this process, but it treats the boundary of a growing shell as rigid and structureless. Here, we extend classical nucleation theory by incorporating thermal fluctuations of the capsid rim using both discrete and continuum descriptions. Allowing the rim of a partially formed capsid to undergo small geometric undulations, we show that these fluctuations generate an entropic contribution that renormalizes the effective line tension. As a result, rim fluctuations can either promote or hinder capsid closure, depending on the subunit-subunit binding free energy, temperature, and fluctuation amplitude. We find that fluctuations generally lower the nucleation barrier when the binding free energy is below a threshold value, while for sufficiently strong binding, they can instead raise the barrier by stabilizing incomplete capsids through a finite-size entropy penalty associated with rim closure. By moving beyond the idealized capillarity approximation, our results provide a controlled extension of classical nucleation theory that clarifies how boundary fluctuations influence capsid nucleation and growth.

cond-mat.soft

Thermodynamic stability and kinetic control of capsid morphologies in hepatitis B virus

Polymorphism has been observed in viral capsid assembly, demonstrating the ability of identical protein dimers to adopt multiple geometries under the same solution conditions. A well-studied example is the hepatitis B virus (HBV), which forms two stable capsid morphologies both in vivo and in vitro. These capsids differ in diameter, containing either 90 or 120 protein dimers. Experiments have shown that their relative prevalence depends on the ionic conditions of the solution during assembly. We developed a model that incorporates salt effects by altering the intermolecular binding free energy between capsid proteins, thereby shifting the relative thermodynamic stability of the two morphologies. This model reproduces experimental results on the prevalence ratios of the large and small HBV capsids. We also constructed a kinetic model that captures the time-dependent ratio of the two morphologies under subcritical capsid concentrations, consistent with experimental data.

physics.bio-ph

An Assembly-Line Mechanism for In-Vitro Encapsulation of Fragmented Cargo in Virus-Like Particles

The ability of virus shells to encapsulate a wide range of functional cargoes, especially multiple cargoes - siRNAs, enzymes, and chromophores - has made them an essential tool in biotechnology for advancing drug delivery applications and developing innovative new materials. Here we present a mechanistic study of the processes and pathways that lead to multiple cargo encapsulation in the co-assembly of virus shell proteins with ligand-coated nanoparticles. Based on the structural identification of different intermediates, enabled by the contrast in electron microscopy provided by the metal nanoparticles that play the cargo role, we find that multiple cargo encapsulation occurs by self-assembly via a specific ``assembly line'' pathway that is different from previously described \emph{in vitro} assembly mechanisms of virus-like particles (VLP). The emerging model explains observations that are potentially important for delivery applications, for instance, the pronounced nanoparticle size selectivity.

cond-mat.soft

Impact of the RNA Binding Domain Localization of the Protein Shell on Virus Particle Stability

The encapsulation of polyanions, whether single-stranded RNAs or synthetic polymers, is primarily driven by attractive electrostatic interactions between the positively charged, structurally disordered RNA-binding domains of virus coat proteins and the negatively charged polyanions. Theoretically, this interaction is often modeled by coarse-graining the charge distribution of the binding domains, either by projecting the charges onto the inner surface of the protein shell or by spreading them across a region representing the capsid lumen where the binding domains are located. In practice, however, the positive charges are not uniformly distributed across the binding domains, which themselves are positioned at discrete, specific sites on the shell surface. Here, we use molecular dynamics simulations to investigate the impact of localized interactions on the most probable or optimal length of the encapsulated polymer, revealing that the specific location of charges along the binding domains plays a significant role, consistent with experimental observations. Comparing the simulations with predictions from a simple mean-field theory taken from the literature, we find that while the general trends are reasonably well captured, quantitative discrepancies arise between the two approaches.

physics.bio-ph

General Solution for Elastic Networks on Arbitrary Curved Surfaces in the Absence of Rotational Symmetry

Understanding crystal growth over arbitrary curved surfaces with arbitrary boundaries is a formidable challenge, stemming from the complexity of formulating non-linear elasticity using geometric invariant quantities. Solutions are generally confined to systems exhibiting rotational symmetry. In this paper, we introduce a framework to address these challenges by numerically solving these equations without relying on inherent symmetries. We illustrate our approach by computing the minimum energy required for an elastic network containing a disclination at any point and by investigating surfaces that lack rotational symmetry. Our findings reveal that the transition from a defect-free structure to a stable state with a single 5-fold or 7-fold disclination strongly depends on the shape of the domain, emphasizing the profound influence of edge geometry. We discuss the implications of our results for general experimental systems, particularly in elucidating the assembly pathways of virus capsids. This research enhances our understanding of crystal growth on complex surfaces and expands its applications across diverse scientific domains.

cond-mat.soft

Switchable Conformation in Protein Subunits: Unveiling Assembly Dynamics of Icosahedral Viruses

The packaging of genetic material within a protein shell, called the capsid, marks a pivotal step in the life cycle of numerous single-stranded RNA viruses. Understanding how hundreds, or even thousands, of proteins assemble around the genome to form highly symmetrical structures remains an unresolved puzzle. In this paper, we design novel subunits and develop a model that enables us to explore the assembly pathways and genome packaging mechanism of icosahedral viruses, which were previously inaccessible. Using molecular dynamics (MD) simulations, we observe capsid fragments, varying in protein number and morphology, assembling at different locations along the genome. Initially, these fragments create a disordered structure that later merges to form a perfect symmetric capsid. The model demonstrates remarkable strength in addressing numerous unresolved issues surrounding virus assembly. For instance, it enables us to explore the advantages of RNA packaging by capsid proteins over linear polymers. Our MD simulations are in excellent agreement with our experimental findings from small-angle X-ray scattering and cryo-transmission electron microscopy, carefully analyzing the assembly products of viral capsid proteins around RNAs with distinct topologies.

physics.bio-ph

Dynamics of elongation of nematic tactoids in an electric field

Nematic tactoids are spindle-shaped droplets of a nematic phase nucleated in the co-existing isotropic phase. According to equilibrium theory, their internal structure and shape are controlled by a balance between the elastic deformation of the director field, induced by the preferred anchoring of that director field to the interface, and the interfacial free energy. Recent experiments on tactoids of chitin nanocrystals dispersed in water show that electrical fields can very strongly elongate tactoids, at least if the tactoids are sufficiently large in volume. However, this observation contradicts the predictions of equilibrium theory as well as findings from Monte Carlo simulations that do not show this kind of extreme elongation to take place at all. To explain this, we put forward a relaxational model based on the Oseen-Frank free energy of elastic deformation of a director field coupled to an anisotropic surface free energy. In our model, we use two reaction coordinates to describe the director field and the extent of elongation of the droplets, and evaluate the evolution of both as a function of time following the switching on of an electric field. Depending on the relative magnitude of the fundamental relaxation rates associated with the two reaction coordinates, we find that the aspect ratio of the drops may develop a large and very long-lived overshoot before eventually relaxing to the much smaller equilibrium value. In that case, the response of the curvature of the director field lags behind, explaining the experimental observations. Our theory describes the experimental data reasonably well.

cond-mat.soft

Biophysical Modeling of SARS-CoV-2 Assembly: Genome Condensation and Budding

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spurred unprecedented and concerted worldwide research to curtail and eradicate this pathogen. SARS-CoV-2 has four structural proteins: Envelope (E), Membrane (M), Nucleocapsid (N), and Spike (S), which self-assemble along with its RNA into the infectious virus by budding from intracellular lipid membranes. In this paper, we develop a model to explore the mechanisms of RNA condensation by structural proteins, protein oligomerization and cellular membrane-protein interactions that control the budding process and the ultimate virus structure. Using molecular dynamics simulations, we have deciphered how the positively charged N proteins interact and condense the very long genomic RNA resulting in its packaging by a lipid envelope decorated with structural proteins inside a host cell. Furthermore, considering the length of RNA and the size of the virus, we find that the intrinsic curvature of M proteins is essential for virus budding. While most current research has focused on the S protein, which is responsible for viral entry, and it has been motivated by the need to develop efficacious vaccines, the development of resistance through mutations in this crucial protein makes it essential to elucidate the details of the viral life cycle to identify other drug targets for future therapy. Our simulations will provide insight into the viral life cycle through the assembly of viral particles de novo and potentially identify therapeutic targets for future drug development.

physics.bio-ph

The dynamics of viruslike capsid assembly and disassembly

Cowpea chlorotic mottle virus (CCMV) is a widely used model for virus replication studies. A major challenge lies in distinguishing between the roles of the interaction between coat proteins and that between the coat proteins and the viral RNA in assembly and disassembly processes. Here, we report on the spontaneous and reversible size conversion of the empty capsids of a CCMV capsid protein functionalized with a hydrophobic elastin-like polypeptide which occurs following a pH jump. We monitor the concentration of T = 3 and T = 1 capsids as a function of time and show that the time evolution of the conversion from one T number to another is not symmetric: the conversion from T = 1 to T = 3 is a factor of 10 slower than that of T = 3 to T = 1. We explain our experimental findings using a simple model based on classical nucleation theory applied to virus capsids, in which we account for the change in the free protein concentration, as the different types of shells assemble and disassemble by shedding or absorbing single protein subunits. As far as we are aware, this is the first study confirming that both the assembly and disassembly of viruslike shells can be explained through classical nucleation theory, reproducing quantitatively results from time-resolved experiments.

physics.bio-ph

Exact Solution for Elastic Networks on Curved Surfaces

The problem of characterizing the structure of an elastic network constrained to lie on a frozen curved surface appears in many areas of science and has been addressed by many different approaches, most notably, extending linear elasticity or through effective defect interaction models. In this paper, we show that the problem can be solved by considering non-linear elasticity in an exact form without resorting to any approximation in terms of geometric quantities. In this way, we are able to consider different effects that have been unwieldy or not viable to include in the past, such as a finite line tension, explicit dependence on the Poisson ratio or the determination of the particle positions for the entire lattice. Several geometries with rotational symmetry are solved explicitly. Comparison with linear elasticity reveals an agreement that extends beyond its strict range of applicability. Implications for the problem of the characterization of virus assembly are also discussed.

physics.bio-ph

Virus Assembly Pathways inside a Host Cell

Simple RNA viruses self-assemble spontaneously and encapsulate their genome into a shell called the capsid. This process is mainly driven by the attractive electrostatic interaction between the positive charges on capsid proteins and the negative charges on the genome. Despite its importance and many decades of intense research, how the virus selects and packages its native RNA inside the crowded environment of a host cell cytoplasm in the presence of an abundance of non-viral RNA and other anionic polymers, has remained a mystery. In this paper, we perform a series of simulations to monitor the growth of viral shells and find the mechanism by which cargo-coat protein interactions can impact the structure and stability of the viral shells. We show that coat protein subunits can assemble around a globular nucleic acid core by forming non-icosahedral cages, which have been recently observed in assembly experiments involving small pieces of RNA. We find that the resulting cages are strained and can easily be split into fragments along stress lines. This suggests that such metastable non-icosahedral intermediates could be easily re-assembled into the stable native icosahedral shells if the larger wild-type genome becomes available, despite the presence of myriad of non-viral RNAs.

physics.bio-ph

Effect of Electric Fields on the Director Field and Shape of Nematic Tactoids

Tactoids are spindle shaped-droplets of a uniaxial nematic phase suspended in the co-existing isotropic phase. They are found in dispersions of a wide variety of elongated colloidal particles, including actin, fd virus, carbon nanotubes, vanadium peroxide and chitin nanocrystals. Recent experiments on tactoids of chitin nanocrystals in water show that electric fields can very strongly elongate tactoids even though the dielectric properties of the co-existing isotropic and nematic phases differ only subtly. We develop a model for partially bipolar tactoids, where the degree of bipolarness of the director field is free to adjust to optimize the sum of the elastic, surface and Coulomb energies of the system. By means of a combination of a scaling analysis and a numerical study, we investigate the elongation and director field's behavior of the tactoids as a function of their size, the strength of the electric field, the surface tension, anchoring strength, the elastic constants and the electric susceptibility anisotropy. We find that tactoids cannot elongate significantly due to an external electric field, unless the director field is bipolar or quasi bipolar and is somehow frozen in the field-free configuration. Presuming that this is the case, we find reasonable agreement with experimental data.

cond-mat.soft

Effect of the charge distribution of virus coat proteins on the length of packaged RNAs

Single-stranded RNA viruses efficiently encapsulate their genome into a protein shell called the capsid. Electrostatic interactions between the positive charges in the capsid protein's N-terminal tail and the negatively charged genome have been postulated as the main driving force for virus assembly. Recent experimental results indicate that the N-terminal tail with the same number of charges and same lengths package different amounts of RNA, which reveals that electrostatics alone cannot explain all the observed outcomes of the RNA self-assembly experiments. Using a mean-field theory, we show that the combined effect of genome configurational entropy and electrostatics can explain to some extent the amount of packaged RNA with mutant proteins where the location and number of charges on the tails are altered. Understanding the factors contributing to the virus assembly could promote the attempt to block viral infections or to build capsids for gene therapy applications.

physics.bio-ph

How a Virus Circumvents Energy Barriers to Form Symmetric Shells

Previous self-assembly experiments on a model icosahedral plant virus have shown that, under physiological conditions, capsid proteins initially bind to the genome through an en masse mechanism and form nucleoprotein complexes in a disordered state, which raises the questions as to how virions are assembled into a highly ordered structure in the host cell. Using small-angle X-ray scattering, we find out that a disorder-order transition occurs under physiological conditions upon an increase in capsid protein concentrations. Our cryo-transmission electron microscopy reveals closed spherical shells containing in vitro transcribed viral RNA even at pH 7.5, in marked contrast with the previous observations. We use Monte Carlo simulations to explain this disorder-order transition and find that, as the shell grows, the structures of disordered intermediates in which the distribution of pentamers does not belong to the icosahedral subgroups become energetically so unfavorable that the caps can easily dissociate and reassemble overcoming the energy barriers for the formation of perfect icosahedral shells. In addition, we monitor the growth of capsids under the condition that the nucleation and growth is the dominant pathway and show that the key for the disorder-order transition in both en masse and nucleation and growth pathways lies in the strength of elastic energy compared to the other forces in the system including protein-protein interactions and the chemical potential of free subunits. Our findings explain, at least in part, why perfect virions with icosahedral order form under different conditions including physiological ones.

physics.bio-ph

Ground States of Crystalline Caps: Generalized Jellium on Curved Space

We study the structure and elastic energy of the ground states of crystalline caps conforming to a spherical surface. These ground states consist of positive disclination defects in structures spanning from flat and weakly curved crystals to closed shells. We compare two different continuum theories and one discrete-lattice approach for the elastic energy of defective caps. We first investigate the transition between defect-free caps to single-disclination ground states and show that it is characterized by continuous symmetry-breaking transition. Further, we show that ground states with icosahedral subgroup symmetries in caps arise across a range of curvatures, even far from the closure point of complete shells. Thus, while superficially similar to other models of 2D `jellium' (e.g. superconducting disks and 2D Wigner crystals), the interplay between the free edge of crystalline caps and the non-Euclidean geometry of its embedding leads to non trivial ground state behaviors, without counterpart in planar jellium models.

cond-mat.soft

Investigation of HIV-1 Gag binding with RNAs and Lipids using Atomic Force Microscopy

Atomic Force Microscopy was utilized to study the morphology of Gag, ΨRNA, and their binding complexes with lipids in a solution environment with 0.1Å vertical and 1nm lateral resolution. TARpolyA RNA was used as a RNA control. The lipid used was phospha-tidylinositol-(4,5)-bisphosphate (PI(4,5)P2). The morphology of specific complexes Gag-ΨRNA, Gag-TARpolyA RNA, Gag-PI(4,5)P2 and PI(4,5)P2-ΨRNA-Gag were studied. They were imaged on either positively or negatively charged mica substrates depending on the net charges carried. Gag and its complexes consist of monomers, dimers and tetramers, which was confirmed by gel electrophoresis. The addition of specific ΨRNA to Gag is found to increase Gag multimerization. Non-specific TARpolyA RNA was found not to lead to an increase in Gag multimerization. The addition PI(4,5)P2 to Gag increases Gag multimerization, but to a lesser extent than ΨRNA. When both ΨRNA and PI(4,5)P2 are present Gag undergoes comformational changes and an even higher degree of multimerization.

q-bio.BM