1P255 Molecular Dynamics Simulation of the Wild-Type and Mutated LOV2 Domains

In this study, a novel monomer aspartokinase (AK) from Corynebacterium pekinense was identified, and its monomer model was constructed. Site 380 was identified by homologous sequencing and monomer model comparison as the key site which was conserved and located around the binding site of the inhibitor Lys. Furthermore, the mutant A380I with enzyme activity 11.32-fold higher than wild type AK (WT-AK), was obtained by site-directed mutagenesis and high throughput screening. In the mutant A380I, the optimal temperature was raised from 26 °C (WT-AK) to 28 °C, the optimal pH remained unchanged at 8.0, and the half-life was prolonged from 4.5 h (WT-AK) to 6.0 h, indicating enhanced thermal stability. The inhibition of A380I was weakened at various inhibitor concentrations and even activated at certain inhibitor concentrations (10 mM of Lys, 5 mM or 10 mM of Lys + Thr, 10 mM of Lys + Met, 5 mM of Lys + Thr + Met). Molecular dynamics simulation results indicated that the occupancy rate of hydrogen bond between A380I and ATP was enhanced, the effect of Lys (inhibitor) on the protein was weakened, and the angle between Ser281-Tyre358 and Asp359-Gly427 was increased after mutation, leading to an open conformation (R-state) that favored the binding of substrate.

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Screening of natural compounds against SOD1 as a therapeutic target for Amyotrophic lateral sclerosis

Letters in Drug Design & Discovery ◽

10.2174/1570180819666211228093736 ◽

2021 ◽

Vol 19 ◽

Author(s):

Sonu Pahal ◽

Amit Chaudhary ◽

Sangeeta Singh

Keyword(s):

Molecular Dynamics ◽

Amyotrophic Lateral Sclerosis ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Virtual Screening ◽

Dynamics Simulation ◽

Pharmacokinetic Parameters ◽

Wild Type ◽

Potential Inhibitors ◽

Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is an uncommon and progressive neurological illness that predominantly includes the neurons liable for voluntary muscular activities. Starting from weakness or stiffness in muscles, this gradually exploits the strength and ability to speak, eat, move and even breathe. Its exact mechanism is still not clear, but mutations in the SOD1 gene have been reported to cause ALS, and some studies also found involvement of SOD1 overexpression in the pathogenesis of ALS. As of now, there is no remedy available for its cure. Objective: To identify the potential inhibitors for wild type 1HL5, l113T mutant, and A4V mutant of SOD1 (Superoxide Dismutase 1) protein. Methods: In this study, in silico approaches like virtual screening, molecular docking, pharmacokinetic parameters study, and molecular dynamics simulation were used to identify the best potential inhibitors against wild type and mutant SOD1 protein. Methods: In this study, in silico approaches like virtual screening, molecular docking, pharmacokinetic parameters study, and molecular dynamics simulation were used to identify the best potential inhibitors against wild type and mutant SOD1 protein. Results: On the basis of binding affinity and binding energy, the top three compounds ZINC000095486263, ZINC000095485989, and ZINC000028462577, were observed as the best compounds. In the case of 1HL5, ZINC000095486263 had the highest binding affinity with docking score -10.62 Kcal/mol, 1UXM with ZINC000095485989 had the highest docking score -12.03 Kcal/mol, and 4A7V with ZINC000028462577 was found -11.72 Kcal/mol. Further, Molecular Dynamic simulations (MDS) results showed that the ZINC000095486263, ZINC000095485989, and ZINC000095485956 compounds were formed a stable complex with 1HL5, 1UXM, and 4A7V, respectively Conclusions: : After analyzing the results, we hereby conclude that naturals compounds such as ZINC000095486263, ZINC000095485989, and ZINC000095485956 could be used as a potential inhibitor of 1HL5, 1UXM, and 4A7V, respectively, for ALS treatment and could be used as a drug. Further, In vivo/vitro study of these compounds could be a future direction in the field of drug discovery.

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Molecular dynamics simulation studies of the wild type and E92Q/N155H mutant of Elvitegravir-resistance HIV-1 integrase

Interdisciplinary Sciences Computational Life Sciences ◽

10.1007/s12539-014-0235-8 ◽

2014 ◽

Cited By ~ 1

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Dynamics Simulation ◽

Simulation Studies ◽

Wild Type ◽

Hiv 1

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Pharmacophore modeling, 3D-QSAR, docking, and molecular dynamics simulation on topoisomerase IV inhibitors of wild type Staphylococcus aureus

Structural Chemistry ◽

10.1007/s11224-017-1056-2 ◽

2017 ◽

Vol 29 (2) ◽

pp. 593-605 ◽

Cited By ~ 2

Author(s):

Srilata Ballu ◽

Ramesh Itteboina ◽

Sree Kanth Sivan ◽

Vijjulatha Manga

Keyword(s):

Molecular Dynamics ◽

Staphylococcus Aureus ◽

Molecular Dynamics Simulation ◽

3D Qsar ◽

Pharmacophore Modeling ◽

Dynamics Simulation ◽

Wild Type ◽

Topoisomerase Iv

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N439K variant in spike protein may alter the infection efficiency and antigenicity of SARS-CoV-2 based on molecular dynamics simulation

10.1101/2020.11.21.392407 ◽

2020 ◽

Author(s):

Wenyang Zhou ◽

Chang Xu ◽

Pingping Wang ◽

Meng Luo ◽

Zhaochun Xu ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Protein Interactions ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Salt Bridge ◽

Dynamics Simulation ◽

Wild Type ◽

Protein Protein Interactions ◽

Angiotensin Converting Enzyme 2

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing an outbreak of coronavirus disease 2019 (COVID-19), has been undergoing various mutations. The analysis of the structural and energetic effects of mutations on protein-protein interactions between the receptor binding domain (RBD) of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) or neutralizing monoclonal antibodies will be beneficial for epidemic surveillance, diagnosis, and optimization of neutralizing agents. According to the molecular dynamics simulation, a key mutation N439K in the SARS-CoV-2 RBD region created a new salt bridge which resulted in greater electrostatic complementarity. Furthermore, the N439K-mutated RBD bound hACE2 with a higher affinity than wild-type, which may lead to more infectious. In addition, the N439K-mutated RBD was markedly resistant to the SARS-CoV-2 neutralizing antibody REGN10987, which may lead to the failure of neutralization. These findings would offer guidance on the development of neutralizing antibodies and the prevention of COVID-19.

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Influence of Disulfide Bridge on the Structural Stability of Human Neuroglobin: A Molecular Dynamics Simulation Using Latest Data Entry

Communications in Physics ◽

10.15625/0868-3166/26/2/8618 ◽

2016 ◽

Vol 26 (2) ◽

pp. 151

Author(s):

Bui Thi Le Quyen ◽

Nguyen Thi Lam Hoai ◽

Ngo Van Thanh

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Structural Stability ◽

Data Entry ◽

Disulfide Bridge ◽

Dynamics Simulation ◽

Wild Type ◽

Heme Group ◽

Classical Simulation

In this paper, we investigated the role of the disulfide bridge in the structural stability of wild-type human neuroglobin. The classical simulation of the neuroglobin without the disulfide bridge was performed for a long simulation run of 240~ns using a new parameter set of Gromos96 force field and the latest data entry as the initial topologies. We used the analyzed data of original neuroglobin with the remained disulfide bridge to compare to the ones from this simulation. Our results showed that, the structure of neuroglobin was still very stable although the disulfide bridge was absent. There was only a few residues in B and C helices having a higher mobility. The most interesting result we obtained was that the increasing distance between the distal histidine and heme group could allow oxygen to bind more easily.

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The Analysis of Hydrophobic Interaction on Aspergillus Niger Xylanase Enzyme Thermal Stability

Journal of Technomaterials Physics ◽

10.32734/jotp.v1i2.1281 ◽

2019 ◽

Vol 1 (2) ◽

pp. 89-98

Author(s):

Nia Daniaty Malau

Keyword(s):

Molecular Dynamics ◽

Thermal Stability ◽

Molecular Dynamics Simulation ◽

Aspergillus Niger ◽

Interaction Analysis ◽

Dynamics Simulation ◽

Simulation Approach ◽

Wild Type ◽

Enzyme Thermal Stability ◽

Xylanase Enzyme

Xylanase is a type of enzyme that has an important role in the industrial field. One measure that can be done to improve the thermostability of an enzyme is by protein engineering. The mutation of the protein can be done by studying protein structures through molecular dynamics simulation approach. In this research, thermal stability analysis on Aspergilus niger Wild Type Xylase (AnX) was performed which aims to study the thermal stability characteristics of xynalase enzyme from Aspergillus niger through molecular dynamics simulation approach. AnX molecular dynamics simulation was performed by NAMD (Not Just Another Molecular Dynamic) software at 300 – 500 K. The research was focused on the study of enzyme thermal stability characteristics in order to get the information of residues accountable for such characteristics. The selection of residues to be mutated was based on hydrophocic interaction analysis. Then from that, the design of xylanase enzyme mutant with better thermostability than wild type xynalase enzyme was made in order to provide design reference for more stable xylanase mutation design which can be implemented in wet experiments for of Aspergillus niger Xylanase enzyme genetic engineering. The enzyme was unfolded at 500 K at 9.5 ns. The residues responsible of the thermal stability were based on hydrophobic interaction analysis in Alanin at residue 60. This residue is located in segmen/chain 3. The best mutant is Alanin 60 residue mutant which is replaced by Methionin and ∆∆Gsolv of -21.10345 was obtained. Thus, Ala60Met is the most stable mutant which might increase the thermal stability of Aspergillus niger Xylanase Enzyme.

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