Capping Mechanism Research Articles

Thermomyces lanuginosus: A prospective thermophilic fungus for green synthesis and stabilization of BioAgNPs through glucoamylase

HypothesisThe rise of bionanoscience has led to the use of silver nanoparticles in therapeutic and industrial applications like biomedicine, biocatalysis, bioremediation and biosensing. Enhancement of metal nanoparticle stability is of critical significance when it comes to safe handling and efficient use of nanoparticles for various applications. In this regard, thermophilic fungi is a potential candidate with their massive thermostable excretome titres. This work aims to explore the potential of thermophilic fungi to provide surface stability to biogenic silver nanoparticles (BioAgNPs). ExperimentThermophilic fungus Thermomyces lanuginosus STm was used to synthesize BioAgNPs. The size and shape of BioAgNPs were characterized using ultraviolet–visible spectroscopy, transmission electron microscopy (TEM) and X-ray diffraction techniques. The most significant process variables affecting mycosynthesis of BioAgNPs were screened using statistical experimental design of Placket Berman model. The mechanism of mycosynthesis and capping on biogenic nanoparticles was explored using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography–mass spectrometry (LC-MS/MS). FindingsCharacterization of BioAgNPs by ultraviolet–visible spectroscopy revealed surface plasmon resonance at 410 nm, X-ray diffraction calculated 7–24 nm diameter of BioAgNPs and transmission electron microscopy showed BioAgNPs to be spherical with 5–35 nm size range. The physico-chemical factors affecting synthesis of BioAgNPs were screened by statistical modeling using Placket Berman experiment design which revealed the significant role of pH and silver precursor salt concentration on BioAgNPs synthesis. The supramolecular bound protein moiety was initially screened using FTIR analysis. The protein coating around BioAgNPs was found to be 67 kDa glucoamylase when detached from NP and investigated using SDS-PAGE and LCMS/MS analysis. In vitro cytotoxic assay against eukaryotic animal model Artemia salina (brine shrimp) larvae revealed dose dependent decrease in viability indicating BioAgNPs to be less cytotoxic, as compared to silver in ionic form. ConclusionGlucoamylase protein (67 kDa) secreted extracellularly by T. lanuginosus STm was discovered to be the capping protein surrounding BioAgNPs. It is interesting to note that in case of BioAgNPs synthesized by extracellular titre of thermophilic fungus, the adsorbed thermostable protein glucoamylase can possibly help in retaining activity of BioAgNPs at elevated temperature as per the industrial requirement. Thus it can be a natural way of immobilization of enzyme on the surface of nanoparticles while eliminating the extra steps require for immobilizing for commercial uses. In terms of acute toxicity, BioAgNPs were found to be less toxic and safer as compared to ionic silver.

The Shr receptor from Streptococcus pyogenes uses a cap and release mechanism to acquire heme–iron from human hemoglobin

Streptococcus pyogenes (group A Streptococcus) is a clinically important microbial pathogen that requires iron in order to proliferate. During infections, S. pyogenes uses the surface displayed Shr receptor to capture human hemoglobin (Hb) and acquires its iron-laden heme molecules. Through a poorly understood mechanism, Shr engages Hb via two structurally unique N-terminal Hb-interacting domains (HID1 and HID2) which facilitate heme transfer to proximal NEAr Transporter (NEAT) domains. Based on the results of X-ray crystallography, small angle X-ray scattering, NMR spectroscopy, native mass spectrometry, and heme transfer experiments, we propose that Shr utilizes a "cap and release" mechanism to gather heme from Hb. In the mechanism, Shr uses the HID1 and HID2 modules to preferentially recognize only heme-loaded forms of Hb by contacting the edges of its protoporphyrin rings. Heme transfer is enabled by significant receptor dynamics within the Shr-Hb complex which function to transiently uncap HID1 from the heme bound to Hb's β subunit, enabling the gated release of its relatively weakly bound heme molecule and subsequent capture by Shr's NEAT domains. These dynamics may maximize the efficiency of heme scavenging by S. pyogenes, enabling it to preferentially recognize and remove heme from only heme-loaded forms of Hb that contain iron.

Will the embedded service in supply chains play a role in lowering manufacturer’s carbon emission and maintaining economic growth?

Introduction: The carbon cap and trade mechanism (CCTM) is forcing companies to reduce carbon emissions. Due to financial and technical constraints, manufacturers responsible for recycling and remanufacturing begin to seek embedded services from energy service companies (ESCOs), marking the emergence of embedded low-carbon service supply chains. The purpose of this paper is to explore the role of embedded low-carbon service in supply chains in lowering manufacturer’s carbon emissions and maintaining economic growth.Methods: In this paper, a decision model for risk-averse closed-loop supply chain for embedded low-carbon service in uncertain markets is built by using the Stackelberg theory and mean-variance (MV) approach. Equilibrium decisions, the manufacturer’s expected utility growth, and total carbon emission reduction are obtained. Sensitivity analysis is performed for the main parameters.Results: The results indicate that only when the manufacturer’s risk aversion level and consumers’ low-carbon preference are within the range of 0.35–0.9, can the manufacturer bring in embedded low-carbon service by cooperating with an ESCO through revenue-sharing contracts. When there is a higher carbon price, embedded low-carbon service can further increase the manufacturer’s expected utility, maintain economic growth and reduce carbon emissions.Discussion: Embedded low-carbon service in supply chains can play a role in lowering manufacturers’ carbon emissions and maintaining economic growth when the manufacturer’s risk aversion level, carbon price, and consumers’ low-carbon preference are high. Theoretically, this study combines closed-loop supply chains (CLSCs) and embedded low-carbon services, enriching supply chain theories. In addition, the findings provide managerial insights for manufacturers, ESCOs, and governments.

Pricing Models for a Two-Period Manufacturing and Remanufacturing Process Under Carbon Cap and Trade Mechanism

Under carbon cap and trade mechanism, collecting ratio and carbon cap seriously affect the decision of a manufacturer in a closed-loop supply chain. This paper constructs pricing models for manufacturing and remanufacturing products in the presence of carbon cap and trade mechanism, aiming to reveal the impact of the collecting ratio for the carbon emission. A manufacturer and a carbon-trade supplier are involved in a Stackelberg pricing game. First, a decision model without carbon trade is formulated. Judging conditions are shown for determining whether carbon cap and collection ratio are effective factors. The two-sided impact of the collection ratio over the carbon emission is demonstrated. In practice, the manufacturer sometimes produces and sells a large proportion of new products by pricing strategies when facing a low collection ratio. Second, a Stackelberg game is played between the manufacturer and the carbon-trade supplier. We demonstrate that the decision model without carbon trade and the game model with carbon trade compose a complete decision process for the manufacturer. Finally, numerical illustrations are designed to examine the sensitivity of the carbon emission with respect to the collection ratio and determine the decision area when both the collection ratio and the carbon cap change.

Intrinsically active capsaicin non-covalently modified nitrogen doped graphene for high-performance supercapacitors

Organic molecules with multi-electron redox active centers exhibit great potential in electrochemical storage. Immobilizing them on the graphene surface through π-π interaction can effectively improve the pseudocapacitance. Nature capsaicin (Cap) molecule, with redox active sites, is good benefit for enhance the capacitance performance of the nitrogen doped graphene (NG) by non-covalent modification. In this work, the Cap-functionalized NG (Cap-NG) is successfully prepared by one-step hydrothermal method combined with vacuum freeze-drying technology. The electrochemical measurements show that the optimal Cap-NG exhibits a high capacitance of 312 F g−1 at 1 Ag−1 and an excellent durable cycling life of 102.9 % after 10,000 charging/discharging cycle times at a current density of 20 Ag−1. Furthermore, the Cap-NG-based symmetrical supercapacitor (SSC) demonstrates an energy density of 8 Wh kg−1 at 596 W kg−1. Moreover, density functional theory (DFT) calculations are used to elaborate the origin of pseudocapacitance by researching the adsorption configuration, binding energy and charge storage mechanism of Cap on NG sheet as well as to calculate the density of states (Dos). This study further enriches the application of natural capsaicin molecule on energy storage, and provides another way to build a green and environment-friendly SCs.

The Socioeconomic Impacts of Emergent Biotechnology on the Next Human Age

Modern biotechnology has progressed to unforeseeable heights, from genetic engineering to radical life extension. The rapid advent of this technology has enforced upon us a duty to contemplate the ethics surrounding it to inform our decisions. One pressing aspect of contemporary bioethics lies in medical developments that have become widely consumed resources. In modern society, big pharmaceutical companies dominate the healthcare industry, which makes them uniquely positioned to introduce new-age biotechnology as consumer resources. A "big pharma" future exemplified by the emergence of revolutionary new-age biotechnology presents severe ethical concerns. This paper describes potential scenarios where emergent biotechnology becomes a consumer resource as a result of aggressive marketing, indirect coercion, and monopoly of the "big pharma" companies. Chasing higher profitability and benefiting from their monopoly position, big pharmaceutical companies can price new biotechnologies at excessive levels, resulting in new biotechnology proliferating along socioeconomic lines. Such a development threatens to create an elite genetic class and destroy social mobility. In order to mitigate such consequences, this paper proposes a price cap mechanism to improve equal access to emerging biotechnology and promote innovations in breakthrough treatments.

The mechanism of RNA capping by SARS-CoV-2

The RNA genome of SARS-CoV-2 contains a 5′ cap that facilitates the translation of viral proteins, protection from exonucleases and evasion of the host immune response1–4. How this cap is made in SARS-CoV-2 is not completely understood. Here we reconstitute the N7- and 2′-O-methylated SARS-CoV-2 RNA cap (7MeGpppA2′-O-Me) using virally encoded non-structural proteins (nsps). We show that the kinase-like nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain5 of nsp12 transfers the RNA to the amino terminus of nsp9, forming a covalent RNA–protein intermediate (a process termed RNAylation). Subsequently, the NiRAN domain transfers the RNA to GDP, forming the core cap structure GpppA-RNA. The nsp146 and nsp167 methyltransferases then add methyl groups to form functional cap structures. Structural analyses of the replication–transcription complex bound to nsp9 identified key interactions that mediate the capping reaction. Furthermore, we demonstrate in a reverse genetics system8 that the N terminus of nsp9 and the kinase-like active-site residues in the NiRAN domain are required for successful SARS-CoV-2 replication. Collectively, our results reveal an unconventional mechanism by which SARS-CoV-2 caps its RNA genome, thus exposing a new target in the development of antivirals to treat COVID-19.

Structure and function of an atypical homodimeric actin capping protein from the malaria parasite

Apicomplexan parasites, such as Plasmodium spp., rely on an unusual actomyosin motor, termed glideosome, for motility and host cell invasion. The actin filaments are maintained by a small set of essential regulators, which provide control over actin dynamics in the different stages of the parasite life cycle. Actin filament capping proteins (CPs) are indispensable heterodimeric regulators of actin dynamics. CPs have been extensively characterized in higher eukaryotes, but their role and functional mechanism in Apicomplexa remain enigmatic. Here, we present the first crystal structure of a homodimeric CP from the malaria parasite and compare the homo- and heterodimeric CP structures in detail. Despite retaining several characteristics of a canonical CP, the homodimeric Plasmodium berghei (Pb)CP exhibits crucial differences to the canonical heterodimers. Both homo- and heterodimeric PbCPs regulate actin dynamics in an atypical manner, facilitating rapid turnover of parasite actin, without affecting its critical concentration. Homo- and heterodimeric PbCPs show partially redundant activities, possibly to rescue actin filament capping in life cycle stages where the β-subunit is downregulated. Our data suggest that the homodimeric PbCP also influences actin kinetics by recruiting lateral actin dimers. This unusual function could arise from the absence of a β-subunit, as the asymmetric PbCP homodimer lacks structural elements essential for canonical barbed end interactions suggesting a novel CP binding mode. These findings will facilitate further studies aimed at elucidating the precise actin filament capping mechanism in Plasmodium.

A robust multi-supplier multi-period inventory model with uncertain market demand and carbon emission constraint

The multi-period inventory management determines the optimal order quantity of products at the beginning of each period, which is an important research issue in supply chain management. In this paper, we propose a robust multi-supplier multi-period inventory model with uncertain market demand and uncertain unit carbon emission in transportation. We select product quality, ordering cost, service level, and emergency capacity as evaluation criteria for each supplier, employ analytic hierarchy process (AHP) technique to comprehensively evaluate and score each supplier. According to the evaluated score, the order weight for each supplier is obtained. In our model, we develop carbon emission constraint based on the carbon cap and carbon trading mechanism. As for uncertain market demand and uncertain unit carbon emission in transportation, we construct Box+Ball and Budget uncertainty sets to characterize various model uncertainties. The robust inventory model is a semi-infinite programming model, and cannot be solved directly. We transform the semi-infinite programming model into a mixed-integer second-order cone-programming (MISOCP) one via cone duality theory. Finally, the effectiveness of the proposed optimization method is illustrated by a case study.

Diplomasi Lingkungan Norwegia kepada Indonesia: Analisis Skema REDD+ tahun 2015-2020

Environmental issues have become a fairly important topic of discussion in the last few decades. These environmental issues have attracted a lot of attention from local to global levels. REDD + contains measures designed to reduce greenhouse gas emissions due to deforestation and forest degradation in the presence of financial incentives. In environmental diplomacy between Indonesia and Norway, the REDD + scheme aims to reduce pollution levels according to targets and within a certain time period. In analyzing Norway's environmental policy and its involvement in global environmental cooperation, market-based environmental policy instruments can be used. In market-based environmental policy instruments there is a carbon trading mechanism to evaluate the REDD + mechanism in 2015-2020. REDD + implementation in Indonesia is carried out with the existence of a carbon market that uses a cap and trade mechanism, which results in the form of carbon credits that can be disbursed into financial incentives. The funds can be used to reduce deforestation and forest degradation, as well as for the conversion of peatlands in Indonesia.

Drivers of the Green Paradox in Europe: An empirical application.

The green paradox describes an undesirable and socially inefficient phenomenon caused by the expansionary reactions of the supply as a response to the various mechanisms that combat climate change. This article seeks to understand and aggregate the different drivers of this phenomenon portrayed in the literature, as well the empirical evidence associated and the proposed solutions. For this purpose, compilation and systematization of the various scientific contributions up to date in this context have been elaborated and the driver's effective impact on the European scenario was evaluated, using a balanced panel for 28 countries in Europe over 1996-2018 and the generalized method of moments (GMM) econometric procedure. Proxies for all provocateurs identified in the state of the art were incorporated in this study: (i) environmental taxes, (ii) green support, (iii) uncertain property rights, (iv) emissions limit (cap), and (v) temporal lag. The dependent variables used are (1) the ratio between the annual production/extraction of oil and the consumption of primary energy and (2) the carbon dioxide (CO2) intensity. We have obtained evidences that the hiatus in the implementation of the European emission cap mechanism has generated a strong green paradox. Moreover, a robust reflection regarding the economic and environmental adequacy of green supports should be considered due to its questionable net benefits. Lastly, we offer some recommendations of public environmental policies that escape the paradoxical phenomenon, through the enunciation of the conditionalities of these provocateurs.

ADP-ribosylation of DNA and RNA

ADP-ribosylation is a chemical modification of macromolecules found across all domains of life and known to regulate a variety of cellular processes. Notably, it has a well-established role in the DNA damage response. While it was historically known as a post-translational modification of proteins, recent studies have shown that nucleic acids can also serve as substrates of reversible ADP-ribosylation. More precisely, ADP-ribosylation of DNA bases, phosphorylated DNA ends and phosphorylated RNA ends have been reported. We will discuss these three types of modification in details. In a variety of bacterial species, including Mycobacterium tuberculosis, ADP-ribosylation of thymidine has emerged as the mode of action of a toxin-antitoxin system named DarTG, with the resultant products perceived as DNA damage by the cell. On the other hand, mammalian DNA damage sensors PARP1, PARP2 and PARP3 were shown to ADP-ribosylate phosphorylated ends of double-stranded DNA in vitro. Additionally, TRPT1 and several PARP enzymes, including PARP10, can add ADP-ribose to the 5’-phosphorylated end of single-stranded RNA in vitro, representing a novel RNA capping mechanism. Together, these discoveries have led to the emergence of a new and exciting research area, namely DNA and RNA ADP-ribosylation, that is likely to have far-reaching implications for the fields of DNA repair, replication and epigenetics.

Emission trading systems and the optimal technology mix

Cap and trade mechanisms enjoy increasing importance in environmental legislations worldwide. One of the important aspects of designing cap and trade mechanisms is the possibility of authorities to grant emission permits for free. Unlike analyzed in the seminal contributions on cap and trade systems, in reality free allocations are not made lump sum, but are updated contingent on firms’ actions, i.e., contingent on production decisions and contingent on facilities entering the market or retiring (see IEA, https://www.oecd-ilibrary.org/content/publication/b7d0842b-en, 2020). As it has already been shown in the literature, such updating yields distorted production decisions of firms (see e.g., Böhringer and Lange in Eur Econ Rev 49(8):2041–2055, 2005, Mackenzie et al. in Environ Resour Econ 39(3):265–282, 2008, or Damon et al. in Rev Environ Econ Policy 13(1):23–42, 2019). The impact of updating on firms’ investment and retiring decisions and the resulting technology mix has received much less attention up to now, however. It is the purpose of the present article to shed light on this aspect and to study the impact of a cap and trade mechanism not only on firms’ output decisions, but also on their investment incentives in different technologies and to analyze the optimal design of emission trading systems in such an environment.

Captopril downregulates expression of Bax/cytochrome C/caspase-3 apoptotic pathway, reduces inflammation, and oxidative stress in cisplatin-induced acute hepatic injury

Cisplatin (Cis) is an effective cancer therapy commonly employed in many therapeutic regimens. However, treatment regimens that contain either a high dose or cumulative doses of Cis could trigger liver damage. A unique study demonstrated that captopril (Cap) protects against Cis-induced liver toxicity, but only some liver function enzymes and some antioxidant enzymes were investigated in that study. Our study aims to elucidate the protective mechanism of Cap against Cis liver toxicity. Acute liver toxicity was induced in rats by injecting a single Cis dose (7.5 mg/kg) in three groups (n = 6). Two groups were pre-treated with low (50 mg/kg) and high (100 mg/kg) Cap doses for one week before Cis injection, and the third group was injected with Cis only. The high Cap dose significantly improved liver function markers (ALT, AST, and ALP) and hepatic tissue pathology. The low Cap dose significantly improved ALP and, to a lesser extent, hepatic tissue pathology. Both Cap doses significantly decreased liver contents of MDA, IL-1β, and cleaved caspase-3; and liver protein expression of TNF-α, Bax, and caspase-3. The high Cap dose significantly increased liver contents of GSH, GPx, CAT, and SOD, and the liver protein expression of Bcl2. Moreover, only the high Cap dose significantly decreased liver IL-6 content and cytochrome C protein expression. Cap did not inhibit the antitumor impact of Cis against HCT116 cancer cells. Therefore, Cap restricts Cis-induced liver toxicity by reducing inflammation and apoptosis and augmenting the antioxidant system.

Structural Basis of SARS-CoV-2 Polymerase Inhibition by Favipiravir

SummaryThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into an unprecedented global pandemic. Nucleoside analogs, such as Remdesivir and Favipiravir, can serve as the first-line broad-spectrum antiviral drugs by targeting the viral polymerases. However, the underlying mechanisms for the antiviral efficacies of these drugs are far from well understood. Here, we reveal that Favipiravir, as a pyrazine derivative, could be incorporated into the viral RNA products by mimicking both adenine and guanine nucleotides. This drug thus inhibits viral replication mainly by inducing mutations in progeny RNAs, different from Remdesivir or other RNA-terminating nucleoside analogs that impair the elongation of RNA products. We further determined the cryo-EM structure of Favipiravir bound to the replicating polymerase complex of SARS-CoV-2 in the pre-catalytic state. This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase, and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues that may explain its capacity for mimicking both adenine and guanine nucleotides. These findings shed light on the mechanism of coronavirus polymerase catalysis and provide a rational basis for developing antiviral drugs to combat the SARS-CoV-2 pandemic.

AtPiezo Plays an Important Role in Root Cap Mechanotransduction.

Plants encounter a variety of mechanical stimuli during their growth and development. It is currently believed that mechanosensitive ion channels play an essential role in the initial perception of mechanical force in plants. Over the past decade, the study of Piezo, a mechanosensitive ion channel in animals, has made significant progress. It has been proved that the perception of mechanical force in various physiological processes of animals is indispensable. However, little is still known about the function of its homologs in plants. In this study, by investigating the function of the AtPiezo gene in the model plant Arabidopsis thaliana, we found that AtPiezo plays a role in the perception of mechanical force in plant root cap and the flow of Ca2+ is involved in this process. These findings allow us to understand the function of AtPiezo from the perspective of plants and provide new insights into the mechanism of plant root cap in response to mechanical stimuli.

MiFID II: the Impact of Double Volume Cap Mechanism on Market Quality

MiFID II: the Impact of Double Volume Cap Mechanism on Market Quality

MiFID II: The Impact of Double Volume Cap Mechanism on Market Quality

I provide a comprehensive evaluation of the Double Volume Cap mechanism, a regulation that regularly triggers dark trading suspension based on a stock's historical dark trading activity. By analysing the impact of each suspension wave occurring between 2018 and 2020, I show that, during the pre-COVID-19 pandemic period, the dark trading suspension improves market liquidity, worsens informational efficiency, and reduces return volatility, whereas, during the post-COVID-19 pandemic period, the suspension imposes exactly opposite effects on market quality. I also find that lifting the dark trading suspension induces exactly opposite impacts, with a larger effect size, compared to triggering suspension, providing more statistically powerful evidence of how dark trading affects market quality. These results imply that the Double Volume Cap mechanism may have brought about many unintended consequences to the market when the market needs liquidity and stability the most and when the suspension is relaxed. Nevertheless, I do identify evidence that the market gradually learns and adapts to the new trading environment as market participants reduce their reliance on dark pools over time, a result consistent with the policymaker's original objective.

The Impact of CPU Voltage Margins on Power-Constrained Execution

CPUs typically operate at a voltage which is higher than what is strictly required, using voltage margins to account for process variability and anticipate any combination of adverse operating conditions. However, these worst-case scenarios occur rarely, if ever, thus the operating voltage is overly pessimistic resulting in excessive power dissipation which leads to decreased performance under power capping. In this paper, we investigate the impact of reducing voltage margins beyond the nominal level on the efficiency of CPU power capping mechanisms, for three commercial systems, two Applied Micro ARMv8 micro-servers (X-Gene2 and X-Gene3) and an Intel x86-64 (Xeon E3). We show that CPU power capping at reduced voltage margins compared with Intel’s RAPL and Dynamic Frequency Scaling (DFS) mechanisms results in performance improvement by up to 64 and 24 percent on average, respectively. In combination with state-of-the-art thread packing, the reduction of CPU voltage margins results in 36, 33 and 27 percent performance improvement compared with RAPL and DFS for the Xeon E3 and the X-Gene processors, respectively. Also, we validate the robustness of our approach with a set of long-running experiments and show that significant energy gains can be achieved even when considering the cost of checkpointing and recovery in large-scale systems.

Computational Investigation of Structural Dynamics of SARS-CoV-2 Methyltransferase-Stimulatory Factor Heterodimer nsp16/nsp10 Bound to the Cofactor SAM.

Recently, a highly contagious novel coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has emerged, posing a global threat to public health. Identifying a potential target and developing vaccines or antiviral drugs is an urgent demand in the absence of approved therapeutic agents. The 5′-capping mechanism of eukaryotic mRNA and some viruses such as coronaviruses (CoVs) are essential for maintaining the RNA stability and protein translation in the virus. SARS-CoV-2 encodes S-adenosyl-L-methionine (SAM) dependent methyltransferase (MTase) enzyme characterized by nsp16 (2′-O-MTase) for generating the capped structure. The present study highlights the binding mechanism of nsp16 and nsp10 to identify the role of nsp10 in MTase activity. Furthermore, we investigated the conformational dynamics and energetics behind the binding of SAM to nsp16 and nsp16/nsp10 heterodimer by employing molecular dynamics simulations in conjunction with the Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) method. We observed from our simulations that the presence of nsp10 increases the favorable van der Waals and electrostatic interactions between SAM and nsp16. Thus, nsp10 acts as a stimulator for the strong binding of SAM to nsp16. The hydrophobic interactions were predominately identified for the nsp16-nsp10 interactions. Also, the stable hydrogen bonds between Ala83 (nsp16) and Tyr96 (nsp10), and between Gln87 (nsp16) and Leu45 (nsp10) play a vital role in the dimerization of nsp16 and nsp10. Besides, Computational Alanine Scanning (CAS) mutagenesis was performed, which revealed hotspot mutants, namely I40A, V104A, and R86A for the dimer association. Hence, the dimer interface of nsp16/nsp10 could also be a potential target in retarding the 2′-O-MTase activity in SARS-CoV-2. Overall, our study provides a comprehensive understanding of the dynamic and thermodynamic process of binding nsp16 and nsp10 that will contribute to the novel design of peptide inhibitors based on nsp16.