ترغب بنشر مسار تعليمي؟ اضغط هنا

Nanomechanical sonification of the 2019-nCoV coronavirus spike protein through a materiomusical approach

566   0   0.0 ( 0 )
 نشر من قبل Markus Buehler
 تاريخ النشر 2020
  مجال البحث فيزياء
والبحث باللغة English
 تأليف Markus J. Buehler




اسأل ChatGPT حول البحث

Proteins are key building blocks of virtually all life, providing the material foundation of spider silk, cells, and hair, but also offering other functions from enzymes to drugs, and pathogens like viruses. Based on a nanomechanical analysis of the structure and motions of atoms and molecules at multiple scales, we report sonifi

قيم البحث

اقرأ أيضاً

134 - Tao Zhou , Quanhui Liu , Zimo Yang 2020
Objectives.--To estimate the basic reproduction number of the Wuhan novel coronavirus (2019-nCoV). Methods.--Based on the susceptible-exposed-infected-removed (SEIR) compartment model and the assumption that the infectious cases with symptoms occurre d before January 25, 2020 are resulted from free propagation without intervention, we estimate the basic reproduction number of 2019-nCoV according to the reported confirmed cases and suspected cases, as well as the theoretical estimated number of infected cases by other research teams, together with some epidemiological determinants learned from the severe acute respiratory syndrome. Results The basic reproduction number falls between 2.8 to 3.3 by using the real-time reports on the number of 2019-nCoV infected cases from Peoples Daily in China, and falls between 3.2 and 3.9 on the basis of the predicted number of infected cases from colleagues. Conclusions.--The early transmission ability of 2019-nCoV is closed to or slightly higher than SARS. It is a controllable disease with moderate-high transmissibility. Timely and effective control measures are needed to suppress the further transmissions. Notes Added.--Using a newly reported epidemiological determinants for early 2019-nCoV, the estimated basic reproduction number is in the range [2.2,3.0].
We present a computational study on the folding and aggregation of proteins in aqueous environment, as function of its concentration. We show how the increase of the concentration of individual protein species can induce a partial unfolding of the na tive conformation without the occurrence of aggregates. A further increment of the protein concentration results in the complete loss of the folded structures and induces the formation of protein aggregates. We discuss the effect of the protein interface on the water fluctuations in the protein hydration shell and their relevance in the protein-protein interaction.
Dynamin is a ubiquitous GTPase that tubulates lipid bilayers and is implicated in many membrane severing processes in eukaryotic cells. Setting the grounds for a better understanding of this biological function, we develop a generalized hydrodynamics description of the conformational change of large dynamin-membrane tubes taking into account GTP consumption as a free energy source. On observable time scales, dissipation is dominated by an effective dynamin/membrane friction and the deformation field of the tube has a simple diffusive behavior, which could be tested experimentally. A more involved, semi-microscopic model yields complete predictions for the dynamics of the tube and possibly accounts for contradictory experimental results concerning its change of conformation as well as for plectonemic supercoiling.
The idea that structural disorder might be a novel mechanism of protein interaction is widespread in the Literature, although the number of statistically significant structural studies supporting this is surprisingly low. At variance with previous wo rks, our conclusions rely exclusively on a large-scale analysis of all the 134337 X-ray crystallographic structures of the Protein Data Bank averaged over clusters of almost identical protein sequences. In this work, we explore the complexity of the organization of all the interaction interfaces observed when a protein lies in alternative complexes, showing that interfaces progressively add up in a hierarchical way. We further investigate the connection of this complexity with different measures of structural disorder: the standard missing residues and a new definition, called soft disorder, that covers all the flexible and structurally amorphous residues of a protein. We show evidences that both the interaction interfaces and the soft disordered regions tend to involve roughly the same amino-acids of the protein, and preliminary results suggesting that soft disorder spots those surface regions where new interfaces are progressively accommodated by complex formation. Our results suggest that disordered regions not only carry crucial information about the location of alternative interfaces within complexes, but also of the order of the assembly. We verify these hypotheses in several examples. We finally compare our measures of disorder with several disorder predictors, showing that these latter are optimized to predict the residues that are missing in all the alternative structures of a protein, and they are not able to catch the progressive evolution of the disordered regions upon complex formation. Yet, the predicted residues, if not missing, tend to be characterized as soft disordered.
Network theory-based approaches provide valuable insights into the variations in global structural connectivity between differing dynamical states of proteins. Our objective is to review network-based analyses to elucidate such variations, especially in the context of subtle conformational changes. We present technical details of the construction and analyses of protein structure networks, encompassing both the non-covalent connectivity and dynamics. We examine the selection of optimal criteria for connectivity based on the physical concept of percolation. We highlight the advantages of using side-chain based network metrics in contrast to backbone measurements. As an illustrative example, we apply the described network approach to investigate the global conformational change between the closed and partially open states of the SARS-CoV-2 spike protein. This conformational change in the spike protein is crucial for coronavirus entry and fusion into human cells. Our analysis reveals global structural reorientations between the two states of the spike protein despite small changes between the two states at the backbone level. We also observe some differences at strategic locations in the structures, correlating with their functions, asserting the advantages of the side-chain network analysis. Finally we present a view of allostery as a subtle synergistic-global change between the ligand and the receptor, the incorporation of which would enhance the drug design strategies.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا