Adsorption-Driven Deformation and Footprints of the RBD Proteins in SARS-CoV-2 Variants on Biological and Inanimate Surfaces.

Respiratory viruses, carried through airborne microdroplets, frequently adhere to surfaces, including plastics and metals. However, our understanding of the interactions between viruses and materials remains limited, particularly in scenarios involving polarizable surfaces. Here, we investigate the role of the receptor-binding domain (RBD) of the spike protein mutations on the adsorption of SARS-CoV-2 to hydrophobic and hydrophilic surfaces employing molecular simulations.

Accurate Boundary Integral Formulations for the Calculation of Electrostatic Forces with an Implicit-Solvent Model.

An accurate force calculation with the Poisson-Boltzmann equation is challenging, as it requires the electric field on the molecular surface. Here we present a calculation of the electric field on the solute-solvent interface that is exact for piecewise linear variations of the potential and analyze four different alternatives to compute the force using a boundary element method. We performed a verification exercise for two cases: the isolated and two interacting molecules.

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.

Quantitative electrostatic force tomography for virus capsids in interaction with an approaching nanoscale probe.

Electrostatic interactions are crucial for the assembly, disassembly and stability of proteinaceous viral capsids. Moreover, at the molecular scale, elucidating the organization and structure of the capsid proteins in response to an approaching nanoprobe is a major challenge in biomacromolecular research. Here, we report on a generalized electrostatic model, based on the Poisson-Boltzmann equation, that quantifies the subnanometric electrostatic interactions between an AFM tip and a proteinaceous capsid from molecular snapshots.

Tuning Contact Angles of Aqueous Droplets on Hydrophilic and Hydrophobic Surfaces by Surfactants.

Adsorption of small amphiphilic molecules occurs in various biological and technological processes, sometimes desired while other times unwanted (e.g., contamination).

Assessing the Stability of Biological Fibrils by Molecular-Scale Simulations.

The nanomechanical characterization of several biological fibrils that are the result of protein aggregation via molecular dynamics simulation is nowadays feasible, and together with atomic force microscopy experiments has widened our understanding of the forces in the regime of pN-nN and system sizes of about hundreds of nanometers. Several methodologies have been developed to achieve this target, and they range from the atomistic representation via molecular force fields to coarse-grained strategies that provide comparable results with experiments in a systematic way. In this chapter, we discuss several methodologies for the calculation of mechanical parameters, such as the elastic constants of relevant biological systems.

RNA Secondary Structures Regulate Adsorption of Fragments onto Flat Substrates.

RNA is a functionally rich molecule with multilevel, hierarchical structures whose role in the adsorption to molecular substrates is only beginning to be elucidated. Here, we introduce a multiscale simulation approach that combines a tractable coarse-grained RNA structural model with an interaction potential of a structureless flat adsorbing substrate. Within this approach, we study the specific role of stem-hairpin and multibranch RNA secondary structure motifs on its adsorption phenomenology.

Structural 3D Domain Reconstruction of the RNA Genome from Viruses with Secondary Structure Models.

Three-dimensional RNA domain reconstruction is important for the assembly, disassembly and delivery functionalities of a packed proteinaceus capsid. However, to date, the self-association of RNA molecules is still an open problem. Recent chemical probing reports provide, with high reliability, the secondary structure of diverse RNA ensembles, such as those of viral genomes.

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).

Quantitative determination of mechanical stability in the novel coronavirus spike protein.

We report on the novel observation about the gain in nanomechanical stability of the SARS-CoV-2 (CoV2) spike (S) protein in comparison with SARS-CoV from 2002 (CoV1). Our findings have several biological implications in the subfamily of coronaviruses, as they suggest that the receptor binding domain (RBD) (∼200 amino acids) plays a fundamental role as a damping element of the massive viral particle's motion prior to cell-recognition, while also facilitating viral attachment, fusion and entry. The mechanical stability via pulling of the RBD is 250 pN and 200 pN for CoV2 and CoV1 respectively, and the additional stability observed for CoV2 (∼50 pN) might play a role in the increasing spread of COVID-19.

Free Energies of the Disassembly of Viral Capsids from a Multiscale Molecular Simulation Approach.

Molecular simulations of large biological systems, such as viral capsids, remains a challenging task in soft matter research. On one hand, coarse-grained (CG) models attempt to make the description of the entire viral capsid disassembly feasible. On the other hand, the permanent development of novel molecular dynamics (MD) simulation approaches, like enhanced sampling methods, attempt to overcome the large time scales required for such simulations.

Mechanical and thermodynamic properties of Aβ, Aβ, and α-synuclein fibrils: a coarse-grained method to complement experimental studies.

We perform molecular dynamics simulation on several relevant biological fibrils associated with neurodegenerative diseases such as Aβ, Aβ, and α-synuclein systems to obtain a molecular understanding and interpretation of nanomechanical characterization experiments. The computational method is versatile and addresses a new subarea within the mechanical characterization of heterogeneous soft materials. We investigate both the elastic and thermodynamic properties of the biological fibrils in order to substantiate experimental nanomechanical characterization techniques that are quickly developing and reaching dynamic imaging with video rate capabilities.

Scalable and fast heterogeneous molecular simulation with predictive parallelization schemes.

Multiscale and inhomogeneous molecular systems are challenging topics in the field of molecular simulation. In particular, modeling biological systems in the context of multiscale simulations and exploring material properties are driving a permanent development of new simulation methods and optimization algorithms. In computational terms, those methods require parallelization schemes that make a productive use of computational resources for each simulation and from its genesis.

Scaling law to determine peak forces in tapping-mode AFM experiments on finite elastic soft matter systems.

Analytical equations to estimate the peak force will facilitate the interpretation and the planning of amplitude-modulation force microscopy (tapping mode) experiments. A closed-form analytical equation to estimate the tip-sample peak forces while imaging soft materials in liquid environment and within an elastic deformation regime has been deduced. We have combined a multivariate regression method with input from the virial-dissipation equations and Tatara's bidimensional deformation contact mechanics model.

Dynamic force microscopy simulator (dForce): A tool for planning and understanding tapping and bimodal AFM experiments.

We present a simulation environment, dForce, which can be used for a better understanding of dynamic force microscopy experiments. The simulator presents the cantilever-tip dynamics for two dynamic AFM methods, tapping mode AFM and bimodal AFM. It can be applied for a wide variety of experimental situations in air or liquid.

Antidiabetic and Renal Protective Properties of Berrycactus Fruit (Myrtillocactus geometrizans).

Native plants are exceedingly valuable because they are sources of natural products with applications for the treatment of various diseases. Berrycactus fruit (Myrtillocactus geometrizans) has been consumed in Mexico since ancient times due to its sweetness. The hypoglycemic and antioxidant effects of this fruit were evaluated in streptozotocin-induced diabetic rats by replacing the drinking water with berrycactus juice (2 or 4 g/kg).

Peak forces and lateral resolution in amplitude modulation force microscopy in liquid.

The peak forces exerted on soft and rigid samples by a force microscope have been modeled by performing numerical simulations of the tip motion in liquid. The forces are obtained by using two contact mechanics models, Hertz and Tatara. We present a comparison between the numerical simulations and three analytical models for a wide variety of probe and operational parameters.

Peak forces in high-resolution imaging of soft matter in liquid.

The maximum force exerted by the tip of a force microscope on the sample surface is a critical factor that determines the spatial resolution and the degree of invasiveness of the measurement, in particular, on soft materials. Here we determine the conditions needed to image soft matter in the 30-500 MPa range while applying very small forces. Imaging at sub-50 pN in the elastic regime can only be achieved under strict conditions in terms of force constant values (below 0.