Biology subjects

Guzman, H. V.

Publications and source records attributed to Guzman, H. V..

4 recordsLinked to original sources

bioRxiv2026

Self-induced Dimensional Reduction and Scaling Transition of mRNA in Polysomes: A Multiscale Simulation Study

The spatial architecture and mechanical rigidity of polysomes are crucial determinants of translational efficiency and mRNA stability. In this study, we investigate the conformational statistics of an mRNA backbone decorated with high-density ribosomes at varying densities using large-scale, extensive molecular dynamics simulations based on the Kremer-Grest bead-spring model. To address the extreme spatial asymmetry between mRNA monomers and ribosomes, we used an efficient tree-based neighbour list algorithm, enabling the analysis of mRNA chains up to N = 4, 969. Our results demonstrate that the excluded volume of massive ribosomes induces a significant and robust expansion of the scaling exponent v from 0.59 to approximately 0.7. In the conformation of mRNA, this shift translates to a self-induced dimensional reduction from a three-dimensional random coil toward a stretched, a quasi-two-dimensional architecture at biologically relevant scales. Such a transition is further evidenced by a periodic "regain" of the bond-bond correlation function C(n) at ribosome attachment sites, indicating a geometric alignment absent in standard homopolymers. These findings reveal that the geometric crowding of ribosomes itself provides a robust physical prerequisite for the formation of higher-order polysome architectures, bridging the gap between polymer physics and structural properties of mRNA during translation.

biophysics↗

bioRxiv2025

2Danalysis: A toolbox for analysis of lipid membranes and biopolymers in two-dimensional space

Molecular simulations expand our ability to learn about the interplay of biomolecules. Biological membranes, composed of diverse lipids with varying physicochemical properties, are highly dynamic environments involved in cellular functions. Proteins, nucleic acids, glycans and bio-compatible polymers are the machinery of cellular processes both in the cytosol and at the lipid membrane interface. Lipid species directly modulate membrane properties, and affect the interaction and function of other biomolecules. Natural molecular diffusion results in changes of local lipid distribution, affecting the membrane properties. Projecting biophysical and structural membrane and biopolymer properties to a two-dimensional plane can be beneficial to quantify molecular signatures in a reduced dimensional space to identify relevant interactions at the interface of interest, i.e. the membrane surface or biopolymer-surface interface. Here, we present a toolbox designed to project membrane and biopolymer properties to a two-dimensional plane to characterize patterns of interaction and spatial correlations between lipid-lipid and lipid-biopolymer interfaces. The toolbox contains two hubs implemented using MDAKits architecture, one for membranes and one for biopolymers, that can be used independently or together. Three case studies demonstrate the versatility of the toolbox with detailed tutorials in GitHub. The toolbox and tutorials will be periodically updated with other functionalities and resolutions to expand our understanding of the structure-function relationship of biomolecules in two-dimensions. SIGNIFICANCE2Danalysis is a significant contribution for the systematic analysis of membrane and biopolymers simulations at planar interfaces. Developed under the open-source MDAKit framework, it enables efficient analysis of trajectories and provides versatile tools for projecting biophysical properties onto a two-dimensional plane. These capabilities enhance the visualization of spatial and temporal changes in membrane characteristics, such as order parameters, and support the study of biopolymer-surface interactions by analyzing adsorption and confinement mechanisms at 2D interfaces. The users can customize the toolbox to study complex 2D phenomena from molecular simulation.

biophysics↗

bioRxiv2021

Single chain models illustrate the 3D RNA folding shape during translation

The three-dimensional conformation of RNA is important in the function and fate of the molecule. The common conformation of mRNA is formed based on the closed-loop structure and internal base pairings with the activity of the ribosome movements. However, recent reports suggest that the closed-loop structure might not be formed in many mRNAs. This implies that mRNA can be considered as a single polymer in the cell. We developed TRIP; Three-dimensional RNA Illustration Program, to model the three-dimensional RNA folding shape based on single-chain models. We identified the angle restriction of each bead component from previously reported single-molecule FISH experimental data. This simulation method was able to recapitulate the mRNA conformation change of the translation activity and three-dimensional positional interaction between organelle and its localized mRNAs. Within the analyzed cases base-pairing interactions only have minor effects on the three-dimensional mRNA conformation, and instead single-chain polymer characteristics have a more significant impact on the conformation. This method will be used to predict the aggregation mechanism of mRNA and long noncoding RNA in specific cellular conditions such as nucleolus and phase-separated granules.

biophysics↗

bioRxiv2020

Characterization of structural and energetic differences between conformations of the SARS-CoV-2 spike protein

The novel coronavirus disease 2019 (COVID-19) pandemic has disrupted modern societies and their economies. The resurgence in COVID-19 cases as part of the second wave is observed across Europe and the Americas. The scientific response has enabled a complete structural characterization of the Severe Acute Respiratory Syndrome - novel Coronavirus 2 (SARS-CoV-2). Among the most relevant proteins required by the novel coronavirus to facilitate the cell entry mechanism is the spike protein trimer. This protein possesses a receptor-binding domain (RBD) that binds the cellular angiotensin-converting enzyme 2 (ACE2) and then triggers the fusion of viral and host cell membranes. In this regard, a comprehensive characterization of the structural stability of the spike protein is a crucial step to find new therapeutics to interrupt the process of recognition. On the other hand, it has been suggested the participation of more than one RBD as a possible mechanism to enhance cell entry. Here we discuss the protein structural stability based on the computational determination of the dynamic contact map and the energetic difference of the spike protein conformations via the mapping of the hydration free energy by the Poisson-Boltzmann method. We expect our result to foster the discussion of the number of RBD involved during recognition and the repurposing of new drugs to disable the recognition by discovering new hotspots for drug targets apart from the flexible loop in the RBD that binds the ACE2.

biophysics↗