Computational Study of Ions and Water Permeation and Transportation Mechanisms of the SARS-CoV-2 Pentameric E Protein Channel

Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus (SARS-CoV-2) and represents the causative agent of a potentially fatal disease that is of public health emergency of international concern. Coronaviruses, including SARS-CoV-2, encode an envelope (E) protein, which is a small, hydrophobic membrane protein; the E protein of SARS-CoV-2 has high homology with that of severe acute respiratory syndrome coronavirus. (SARS-CoV) In this study, we provide insights into the function of the SARS-CoV-2 E protein channel and the ion and water permeation mechanisms on the basis of combined in silico methods. Our results suggest that the pentameric E protein promotes the penetration of monovalent ions through the channel. Analysis of the potential mean force (PMF), pore radius and diffusion coefficient reveals that Leu10 and Phe19 are the hydrophobic gates of the channel. In addition, the pore demonstrated a clear wetting/dewetting transition with monovalent cation selectivity under transmembrane voltage, which indicates that it is a hydrophobic voltage-dependent channel. Overall, these results provide structural-basis insights and molecular-dynamic information that are needed to understand the regulatory mechanisms of ion permeability in the pentameric SARS-CoV-2 E protein channel.

alphaIIbbeta3 modeling simulation and design of the cyclic RGD / 生物工程学报

Integrin alphaIIbbeta3 of the platelet surfaces regulates the thrombosis formation. alphaIIbbeta3 binds to the RGD sequence (Arg-Gly-Asp) of fibrinogen, promotes the platelet aggregation and finally leads to the thrombus. We obtained the three-dimensional molecular structure of alphaIIbbeta3 using homology-modeling (modeller8v2 software), with integrin alphavbeta3 (pdb code 1JV2) as the template. Accordingly, a cyclic RGD(RGD-c) peptide was designed to bind alphaIIbbeta3 as an antagonist and to block the formation of thrombus. We added two amino acids X, Y to both sides of RGD-c. X and Y could bind to each other by disulfide bond that finally made RGD-c a cyclic peptide. The optimum structure of RGD-c was obtained from the energetic optimization processes. All amino acids were placed at the X and Y to conduct Molecular Docking to the integrin alphaIIbbeta3 We got the optimum structure of RGD-c by energetic optimization and the antagonistic combination analysis. The results might provide an insight into designing and screening integrin alphaIIbbeta3 antagonists.