A Coarse-Grained Model for the Mechanical Behavior of Na-Montmorillonite Clay.

Sodium montmorillonite (Na-MMT) is one of the most commonly found swelling clay minerals with diverse engineering and technological applications. The nanomechanical properties of this mineral have been extensively investigated computationally utilizing molecular dynamics (MD) simulations to portray the molecular-level changes at different environmental conditions. As the environmentally found Na-MMT clays are generally sized within hundreds of nanometers, all-atomistic (AA) MD simulations of clays within such size range are particularly challenging due to computational inefficiency. Informed from atomistic modeling, a coarse-grained (CG) modeling technique can be employed to overcome the spatiotemporal limitation. The current study presents a modeling strategy to develop a computationally efficient model of Na-MMT clay with a typical size over ≃100 nm by shrinking the atomistic platelet thickness and reducing the number of center-layer atoms. Using the "strain-energy conservation" approach, the force field parameters for the CG model are obtained and the developed CG model can well preserve in-plane tension, shear, and bending behaviors of atomistic counterparts. Remarkably, the CG tactoid model of Na-MMT, a hierarchical multilayer structure, can reproduce the interlayer shear and adhesion as well as d-spacing among the clay sheets as of atomistic one to a good approximation while gaining significantly improved computational speed. Our study demonstrates the efficacy of the CG modeling framework, paving the way for the bottom-up multiscale prediction of mechanical behaviors of clay and related minerals.

Dissociation Mechanisms of G-actin Subunits Govern Deformation Response of Actin Filament.

Actin molecules are essential structural components of the cellular cytoskeleton. Here, we report a comprehensive analysis of F-actin's deformation behavior and highlight underlying mechanisms using steered molecular dynamics simulations (SMD). The investigation of F-actin was done under tension, compression, bending, and torsion. We report that the dissociation pattern of conformational locks at intrastrand and interstrand G-actin interfaces regulates the deformation response of F-actin. The conformational locks at the G-actin interfaces are portrayed by a spheroidal joint, interlocking serrated plates' analogy. Further, the SMD simulation approach was utilized to evaluate Young's modulus, flexural rigidity, persistent length, and torsional rigidity of F-actin, and the values obtained were found to be consistent with available experimental data. The evaluation of the mechanical properties of actin and the insight into the fundamental mechanisms contributing to its resilience described here are necessary for developing accurate models of eukaryotic cells and for assessing cellular viability and mobility.

Binding of SARS-COV-2 (COVID-19) and SARS-COV to human ACE2: Identifying binding sites and consequences on ACE2 stiffness.

The SARS-CoV-2 coronavirus (COVID-19) that is causing the massive global pandemic exhibits similar human cell invasion mechanism as the coronavirus SARS-CoV, which had significantly lower fatalities. The cell membrane protein Angiotensin-converting enzyme 2 (ACE2) is the initiation point for both the coronavirus infections in humans. Here, we model the molecular interactions and mechanical properties of ACE2 with both SARS-CoV and COVID-19 spike protein receptor-binding domains (RBD). We report that the COVID-19 spike RBD interacts with ACE2 more strongly and at only two protein residues, as compared to multi-residue interaction of the SARS-CoV. Although both coronaviruses stiffen the ACE2, the impact of COVID-19 is six times larger, which points towards differences in the severity of the reported respiratory distress. The recognition of specific residues of ACE2 attachments to coronaviruses is important as the residues suggest potential sites of intervention to inhibit attachment and subsequent entry of the COVID-19 into human host cells.

Differences in Interactions Within Viral Replication Complexes of SARS-CoV-2 (COVID-19) and SARS-CoV Coronaviruses Control RNA Replication Ability.

COVID-19 has become a global pandemic caused by the SARS-CoV-2 coronavirus. SARS-CoV-2 shares many similarities with SARS coronavirus (SARS-CoV). A viral replication complex containing non-structural proteins (nsps) is the toolbox for RNA replication and transcription of both coronaviruses. In both cases, the RNA-dependent RNA polymerase (RdRp) domain of the coronaviral replication complex dictates the primary polymerase activity by cooperating with cofactors. The higher transmissibility and mortality due to SARS-CoV-2 are related to its higher RNA replication activity compared to SARS-CoV. The discrepancy between the RNA replication efficiency of SARS-CoV and SARS-CoV-2 can be understood by exploring interactions within their viral replication complexes. Our modeling of molecular interactions within the viral replication complexes of SARS-CoV and SARS-CoV-2 using molecular dynamics simulations suggests that in contrast to SARS-CoVnsp12, SARS-CoV2nsp12 prefers helices as the dominant interacting secondary motifs. The relative differences in nonbonded interactions between nsps could suggest viral RNA replication ability in coronaviruses. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11837-021-04662-6.