scholarly journals Insights from MD Simulation on Na+ Binding and Loop Dynamics in Multidrug Resistance Transporter Norm

2018 ◽  
Author(s):  
Jun Jun Du ◽  
GuanFu Duan ◽  
Changge Ji ◽  
Jianing Song ◽  
J.Z.H. Zhang
Keyword(s):  
Multidrug Resistance ◽  
Conformational Changes ◽  
Simulation Study ◽  
Critical Role ◽  
Cation Binding ◽  
Dynamics Simulation ◽  
Multi Stage ◽  
Cation Binding Site ◽  
Releasing Process ◽  
Multidrug Resistance Transporter

The multidrug resistance transporter NorM is an important drug resistance pump and plays a critical role in multidrug resistance in bacteria and mammals. In this study we carried out molecular dynamics simulation to study the mechanism of Na+ binding and dynamical structures of two long loops in the substrate-releasing process in substrate binding NorM. Our simulation study identified several key residues (D41, E261 D377) along the Na+ binding pathway and a multi-state ion-binding mechanism is proposed based on the simulation study. In this proposed model, the transport of Na+ is a multi-stage process with D41 being the first station for binding to Na+, followed by Na+ binding to the second station E262 and finally to the cation-binding site of E262 and D377. During the transport of Na+, the transmembrane components TM1, TM7 and TM2 are rearranged to facilitate the ion transport as well conformational changes of NorM to a closed state. Further, substrate-bound simulation revealed that Loop3-4 and Loop9-10 control the substrate-releasing process.

scholarly journals Computational Approach for Structural Feature Determination of Grapevine NHX Antiporters

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Mariem Ayadi ◽  
Rayda Ben Ayed ◽  
Rim Mzid ◽  
Sami Aifa ◽  
Mohsen Hanana
Keyword(s):  
Posttranslational Modifications ◽  
Ph Regulation ◽  
Critical Role ◽  
3D Structure ◽  
Monovalent Cation ◽  
Cation Binding ◽  
Cation Binding Site ◽  
C Terminus ◽  
Group I ◽  
Tm Domain

Plant NHX antiporters are responsible for monovalent cation/H+ exchange across cellular membranes and play therefore a critical role for cellular pH regulation, Na+ and K+ homeostasis, and salt tolerance. Six members of grapevine NHX family (VvNHX1-6) have been structurally characterized. Phylogenetic analysis revealed their organization in two groups: VvNHX1-5 belonging to group I (vacuolar) and VvNHX6 belonging to group II (endosomal). Conserved domain analysis of these VvNHXs indicates the presence of different kinds of domains. Out of these, two domains function as monovalent cation-proton antiporters and one as the aspartate-alanine exchange; the remaining are not yet with defined function. Overall, VvNHXs proteins are typically made of 11-13 putative transmembrane regions at their N-terminus which contain the consensus amiloride-binding domain in the 3rd TM domain and a cation-binding site in between the 5th and 6th TM domain, followed by a hydrophilic C-terminus that is the target of several and diverse regulatory posttranslational modifications. Using a combination of primary structure analysis, secondary structure alignments, and the tertiary structural models, the VvNHXs revealed mainly 18 α helices although without β sheets. Homology modeling of the 3D structure showed that VvNHX antiporters are similar to the bacterial sodium proton antiporters MjNhaP1 (Methanocaldococcus jannaschii) and PaNhaP (Pyrococcus abyssi).

Zn2+ion of the snake venom metalloproteinase (SVMP) plays a critical role in ligand binding: a molecular dynamics simulation study

RSC Advances ◽  
2015 ◽  
Vol 5 (86) ◽  
pp. 70566-70576 ◽  
Author(s):  
Sathishkumar Chinnasamy ◽  
Selvaraman Nagamani ◽  
Karthikeyan Muthusamy
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Ligand Binding ◽  
Blood Coagulation ◽  
Snake Venom ◽  
Simulation Study ◽  
Tissue Damage ◽  
Critical Role ◽  
Dynamics Simulation ◽  
Snake Venom Metalloproteinase

Snake venom metalloproteinase (SVMP) is one of the major components of snake venom and it is a root causative agent for edema, local tissue damage, inflammation, blood coagulation and hemorrhage during the snake bite.

scholarly journals Alkaloids and flavonoids from African phytochemicals as potential inhibitors of SARS-Cov-2 RNA-dependent RNA polymerase: an in silico perspective

2020 ◽  
Vol 28 ◽  
pp. 204020662098407
Author(s):  
Oludare M Ogunyemi ◽  
Gideon A Gyebi ◽  
Abdo A Elfiky ◽  
Saheed O Afolabi ◽  
Olalekan B Ogunro ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Active Sites ◽  
Virus Disease ◽  
Experimental Studies ◽  
Cation Binding ◽  
Dynamics Simulation ◽  
Amino Acid Residues ◽  
Rna Dependent Rna Polymerase ◽  
Cation Binding Site ◽  
Positive Controls

Corona Virus Disease 2019 (COVID-19) is a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Exploiting the potentials of phytocompounds is an integral component of the international response to this pandemic. In this study, a virtual screening through molecular docking analysis was used to screen a total of 226 bioactive compounds from African herbs and medicinal plants for direct interactions with SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). From these, 36 phytocompounds with binding affinities higher than the approved reference drugs (remdesivir and sobosivir), were further docked targeting the active sites of SARS-CoV-2, as well as SARS-CoV and HCV RdRp. A hit list of 7 compounds alongside two positive controls (remdesivir and sofosbuvir) and two negative controls (cinnamaldehyde and Thymoquinone) were further docked into the active site of 8 different conformations of SARS-CoV-2 RdRp gotten from molecular dynamics simulation (MDS) system equilibration. The top docked compounds were further subjected to predictive druglikeness and ADME/tox filtering analyses. Drugable alkaloids (10’–hydroxyusambarensine, cryptospirolepine, strychnopentamine) and flavonoids (usararotenoid A, and 12α-epi-millettosin), were reported to exhibit strong affinity binding and interactions with key amino acid residues in the catalytic site, the divalent-cation–binding site, and the NTP entry channel in the active region of the RdRp enzyme as the positive controls. These phytochemicals, in addition to other promising antivirals such as remdesivir and sofosbuvir, may be exploited towards the development of a cocktail of anti-coronavirus treatments in COVID-19. Experimental studies are recommended to validate these study.

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