Electrostatic features for nucleocapsid proteins of SARS-CoV and SARS-CoV-2

Abstract

COVID-19 is increasingly affecting human health and global economy. Understanding the fundamental mechanisms of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is highly demanded to develop treatments for COVID-19. SARS-CoV and SARS-CoV-2 share 92.06% identity in their N protein RBDs’ sequences, which results in very similar structures. However, the SARS-CoV-2 is more easily to spread. Utilizing multi-scale computational approaches, this work studied the fundamental mechanisms of the nucleocapsid (N) proteins of SARS-CoV and SARS-CoV-2, including their stabilities and binding strengths with RNAs at different pH values. Electrostatic potential on the surfaces of N proteins show that both the N proteins of SARS-CoV and SARS-CoV-2 have dominantly positive potential to attract RNAs. The binding forces between SARS-CoV N protein and RNAs at different distances are similar to that of SARS-CoV-2, both in directions and magnitudes. The electric filed lines between N proteins and RNAs are also similar for both SARS-CoV and SARS-CoV-2. The folding energy and binding energy dependence on pH revealed that the best environment for N proteins to perform their functions with RNAs is the weak acidic environment.

Using a comprehensive approach to investigate the interaction between Kinesin-5/Eg5 and the microtubule

“…Even though many efforts have been undertaken to study molecular motors [33] , [34] , the mechanisms of kinesin motility on microtubules are still not completely characterized. In addition to in vivo and in vitro approaches, computational methods have been widely used to study the functions of biomolecules [35] , [36] , [37] , [38] , [39] , [40] , [41] . In this work, we used a multi-scale computational approach that combines DelPhi [42] , [43] , DelPhiForce [44] , [45] , DelPhiPKa [46] , [47] and NAMD [48] to study the binding mechanism of Eg5 to the microtubule.…”

Computational Study on DNA Repair: The Roles of Electrostatic Interactions Between Uracil-DNA Glycosylase (UDG) and DNA

“…Since UDG targets uracil in a real DNA base rather than P2U, we mutated the P2U base to uracil (U) using Chimera. We deleted all the water molecules that are involved in the original structures, as DelPhi (Li et al, 2012), DelPhiForce (Li et al, 2017a), and DelPhiPKa (Wang et al, 2015b) implement an implicit solvent model (Poisson-Boltzmann) in the calculations, which have been proved to be successful in previous studies (Jia et al, 2017;Xie et al, 2020a;Xie et al, 2020b;Guo et al, 2021;Lopez-Hernandez et al, 2021).…”

The pH Effects on SARS-CoV and SARS-CoV-2 Spike Proteins in the Process of Binding to hACE2

“…The traditional process of the de novo drug design is a challenging task that consumes resources and time significantly. With the fast developments of computing technology, computational methods have been widely used in drug-related research [12], including protein-protein interactions [13,14], MD simulations [15], coarse-grained models [16], pH dependence of protein-protein interactions [17][18][19][20], etc. Our previous studies have applied multi-scale computational methods to study several pathogens [21][22][23][24][25] including the SARS-CoV-2 viruses [26,27], which revealed some mechanisms of the SARS-CoV-2 S protein.…”