scholarly journals Substrate binding and translocation of the serotonin transporter studied by docking and molecular dynamics simulations

2011 ◽  
Vol 18 (3) ◽  
pp. 1073-1085 ◽  
Author(s):  
Mari Gabrielsen ◽  
Aina Westrheim Ravna ◽  
Kurt Kristiansen ◽  
Ingebrigt Sylte
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Serotonin Transporter ◽  
Substrate Binding ◽  
Dynamics Simulations

A molecular dynamics study of the complete binding process of meropenem to New Delhi metallo-β-lactamase 1

2018 ◽  
Vol 20 (9) ◽  
pp. 6409-6420 ◽  
Author(s):  
Juan Duan ◽  
Chuncai Hu ◽  
Jiafan Guo ◽  
Lianxian Guo ◽  
Jia Sun ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Substrate Binding ◽  
New Delhi ◽  
Binding Process ◽  
Dynamics Simulations

We have investigated the substrate-binding pathways of NDM-1 via unbiased molecular dynamics simulations and metadynamics.

scholarly journals Ligand Induced Conformational Changes of the Human Serotonin Transporter Revealed by Molecular Dynamics Simulations

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e63635 ◽  
Author(s):  
Heidi Koldsø ◽  
Henriette Elisabeth Autzen ◽  
Julie Grouleff ◽  
Birgit Schiøtt
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Serotonin Transporter ◽  
Conformational Changes ◽  
Dynamics Simulations

scholarly journals Substrate Binding at the Qo-Site of the Bacterial Cytochrome bc1 Complex Predicted by Atomistic Molecular Dynamics Simulations

2013 ◽  
Vol 104 (2) ◽  
pp. 490a
Author(s):  
Pekka A. Postila ◽  
Karol Kaszuba ◽  
Marcin Sarewicz ◽  
Artur Osyczka ◽  
Ilpo Vattulainen ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Substrate Binding ◽  
Cytochrome Bc1 ◽  
Bc1 Complex ◽  
Cytochrome Bc1 Complex ◽  
Qo Site ◽  
Dynamics Simulations

scholarly journals ROLE OF SUBSTRATE BINDING ON THE PROTEIN DYNAMICS OF AN ENDOGLUCANASE FROM FUSARIUM OXYSPORUM AT DIFFERENT TEMPERATURES

2018 ◽  
Vol 19 (1) ◽  
pp. 307-314
Author(s):  
ABDUL AZIZ AHMAD ◽  
Hamzah Mohd. Salleh ◽  
IBRAHIM ALI NOORBATCHA
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Fusarium Oxysporum ◽  
Protein Dynamics ◽  
Substrate Binding ◽  
Solvent Accessible Surface Area ◽  
Enzyme Complex ◽  
Different Temperatures ◽  
Endoglucanase I ◽  
Dynamics Simulations

: Thermostability is an important requirement for protein function, and one goal of protein engineering is improvement of activity of the enzymes at higher temperatures, particularly for industrial applications. Computational approaches to investigate factors influencing thermostability of proteins are becoming researchers’ choice. This study investigates the influence of substrate binding on the protein dynamics by comparing the molecular dynamics simulations of substrate-enzyme complex against un-bound enzyme, using endoglucanase I from Fusarium oxysporum. Endoglucanase-substrate complex was prepared by docking and molecular dynamics simulations were carried out at three different temperatures, 313 K, 333 K and 353 K. Our finding shows that the secondary structures for substrate-enzyme complex show more fluctuations relative to un-complexed structure. The same trend was observed for solvent accessible surface area and radius of gyration. At the highest temperature studied (353 K), the substrate-enzyme complex form showed the highest fluctuations. The fluctuations around the active site regions reach a minimum at the optimum temperature, compared to the other structural regions and other temperatures. ABSTRAK: Kestabilan (ketahanan) terhadap haba merupakan keperluan yang penting untuk fungsi protin, salah satu matlamat kejuruteraan protin adalah penambahbaikan aktiviti enzim pada suhu yang tinggi khususnya untuk aplikasi industri. Kini para penyelidik memilih kaedah komputasi, bagi mengkaji faktor yang mempengaruhi kestabilan terhadap haba. Kajian ini menyelidik pengaruh ikatan substrat pada protin dengan membandingkan simulasi molekular dinamik diantara substrat-enzim kompleks dan enzim sahaja, menggunakan endoglucanase I dari Fusarium oxysporum. Kompleks endoglucanase-substrat disediakan melalui kaedah docking dan simulasi molekular dinamik dilakukan pada suhu 313 K, 333 K dan 353 K. Kajian kami menunjukkan struktur sekunder bagi substrat-enzim kompleks kurang stabil berbanding enzim sahaja. Pola yang sama bagi luas permukaan boleh dicapai pelarut (SASA) dan jejari gyrasi. Pada suhu tertinggi dikaji (353 K), substrat-enzim kompleks paling tidak stabil. Pada suhu optimum, kadar ubah-ubah sekitar amino asid aktif adalah minimum berbanding struktur dan suhu lain.  

scholarly journals Structural Differences In 3C-like protease (Mpro) From SARS-CoV and SARS-CoV-2: Molecular Insights For Drug Repurposing Against COVID-19 Revealed by Molecular Dynamics Simulations.

2021 ◽  
Author(s):  
Dhaval Patel ◽  
Meet Parmar ◽  
Ritik Thumar ◽  
Bhumi Patel ◽  
Mohd. Athar ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Binding Site ◽  
Active Site ◽  
Substrate Binding ◽  
Drug Repurposing ◽  
Molecular Networks ◽  
Substrate Binding Site ◽  
Sequence Identity ◽  
Dynamics Simulations

A recent fatal outbreak of novel coronavirus SARS-CoV-2, identified preliminary as a causative agent for series of unusual pneumonia cases in Wuhan city, China has infected more than 20 million individuals with more than 4 million mortalities. Since, the infection crossed geographical barriers, the WHO permanently named the causing disease as COVID-2019 by declaring it a pandemic situation. SARS-CoV-2 is an enveloped single-stranded RNA virus causing a wide range of pathological conditions from common cold symptoms to pneumonia and fatal severe respiratory syndrome. Genome sequencing of SARS-CoV-2 has revealed 96% identity to the bat coronavirus and 79.6% sequence identity to the previous SARS-CoV. The main protease (known as 3C-like proteinase/ Mpro) plays a vital role during the infection with the processing of replicase polyprotein thus offering an attractive target for therapeutic interventions. SARS-CoV and SARS-CoV-2 Mpro shares 97% sequence identity, with 12 variable residues but none of them are present in the catalytic and substrate binding site. With the high level of sequence and structural similarity and absence of any drug/vaccine against SARS-CoV-2, drug repurposing against Mpro is an effective strategy to combat COVID-19. Here, we report a detailed comparison of SARS-CoV-2 Mpro with SARS-CoV Mpro using molecular dynamics simulations to assess the impact of 12 divergent residues on the molecular microenvironment of Mpro. Structural comparison and analysis are made on how these variable residues affect the intra-molecular interactions between key residues in the monomer and biologically active dimer form of Mpro. The present MD simulations study concluded the change in microenvironment of active-site residues at the entrance (T25, T26, M49 and Q189), near the catalytic region (F140, H163, H164, M165 and H172) and other residues in substrate binding site (V35T, N65S, K88R and N180K) due to 12 mutation incorporated in the SARS-CoV-2 Mpro. It is also evident that SARS-CoV-2 dimer is more stable and less flexible state compared to monomer which may be due to these variable residues, mainly F140, E166 and H172 which are involved in dimerization. This also warrants a need for inhibitor design considering the more stable dimer form. The mutation accumulated in SARS-CoV-2 Mpro indirectly reconfigures the key molecular networks around the active site conferring a potential change in SARS-CoV-2, thus posing a challenge in drug repurposing SARS drugs for COVID-19. The new networks and changes in the microenvironment identified by our work might guide attempts needed for repurposing and identification of new Mpro inhibitors.

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