The Tinker software, currently released as version 8, is a modular molecular mechanics and dynamics package written primarily in a standard, easily portable dialect of Fortran 95 with OpenMP extensions It supports a wide variety of force fields, including polarizable models such as the Atomic Multipole Optimized Energetics for Biomolecular Applications (AMOEBA) force field The package runs on Linux, macOS, and Windows systems In addition to canonical Tinker, there are branches, Tinker-HP and Tinker-OpenMM, designed for use on message passing interface (MPI) parallel distributed memory supercomputers and state-of-the-art graphical processing units (GPUs), respectively The Tinker suite also includes a tightly integrated Java-based graphical user interface called Force Field Explorer (FFE), which provides molecular visualization capabilities as well as the ability to launch and control Tinker calculations

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Tinker 8: Software Tools for Molecular Design.

Recognition of injured mitochondria for degradation by macroautophagy is essential for cellular health, but the mechanisms remain poorly understood Cardiolipin is an inner mitochondrial membrane phospholipid We found that rotenone, staurosporine, 6-hydroxydopamine and other pro-mitophagy stimuli caused externalization of cardiolipin to the mitochondrial surface in primary cortical neurons and SH-SY5Y cells RNAi knockdown of cardiolipin synthase or of phospholipid scramblase-3, which transports cardiolipin to the outer mitochondrial membrane, decreased the delivery of mitochondria to autophagosomes Furthermore, we found that the autophagy protein microtubule-associated-protein-1 light chain 3 (LC3), which mediates both autophagosome formation and cargo recognition, contains cardiolipin-binding sites important for the engulfment of mitochondria by the autophagic system Mutation of LC3 residues predicted as cardiolipin-interaction sites by computational modelling inhibited its participation in mitophagy These data indicate that redistribution of cardiolipin serves as an 'eat-me' signal for the elimination of damaged mitochondria from neuronal cells

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Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells

Molecular Dynamics

The papain-like protease PLpro is an essential coronavirus enzyme that is required for processing viral polyproteins to generate a functional replicase complex and enable viral spread1,2. PLpro is also implicated in cleaving proteinaceous post-translational modifications on host proteins as an evasion mechanism against host antiviral immune responses3-5. Here we perform biochemical, structural and functional characterization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PLpro (SCoV2-PLpro) and outline differences with SARS-CoV PLpro (SCoV-PLpro) in regulation of host interferon and NF-κB pathways. SCoV2-PLpro and SCoV-PLpro share 83% sequence identity but exhibit different host substrate preferences; SCoV2-PLpro preferentially cleaves the ubiquitin-like interferon-stimulated gene 15 protein (ISG15), whereas SCoV-PLpro predominantly targets ubiquitin chains. The crystal structure of SCoV2-PLpro in complex with ISG15 reveals distinctive interactions with the amino-terminal ubiquitin-like domain of ISG15, highlighting the high affinity and specificity of these interactions. Furthermore, upon infection, SCoV2-PLpro contributes to the cleavage of ISG15 from interferon responsive factor 3 (IRF3) and attenuates type I interferon responses. Notably, inhibition of SCoV2-PLpro with GRL-0617 impairs the virus-induced cytopathogenic effect, maintains the antiviral interferon pathway and reduces viral replication in infected cells. These results highlight a potential dual therapeutic strategy in which targeting of SCoV2-PLpro can suppress SARS-CoV-2 infection and promote antiviral immunity.

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Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity.

We used force-field-based molecular dynamics to study the interaction between polymers and carbon nanotubes (CNTs). The intermolecular interaction energy between single-walled carbon nanotubes and polymers was computed, and the morphology of polymers adsorbed to the surface of nanotubes was investigated. Furthermore, the "wrapping" of nanotubes by polymer chains was examined. It was found that the specific monomer structure plays a very important role in determining the strength of interaction between nanotubes and polymers. The results of our study suggest that polymers with a backbone containing aromatic rings are promising candidates for the noncovalent binding of carbon nanotubes into composite structures. Such polymers can be used as building blocks in amphiphilic copolymers to promote increased interfacial binding between the CNT and a polymeric matrix.

Interactions between polymers and carbon nanotubes: a molecular dynamics study.

We derive equilibrium fluctuation expressions for the linear response of many body systems thermostated by the Nose–Hoover thermostat. We show that in the thermodynamic limit this response is the same as that of the corresponding Gaussian isothermal system. Numerical comparisons for shear flow show however that the Gaussian methods provide a significantly more efficient means of calculating the shear viscosity coefficient.

B. L. Holian

Papers

The Nose–Hoover thermostat