scholarly journals Understanding the R882H mutation effects of DNA methyltransferase DNMT3A: a combination of molecular dynamics simulations and QM/MM calculations

RSC Advances ◽  
2019 ◽  
Vol 9 (54) ◽  
pp. 31425-31434 ◽  
Author(s):  
Lanxuan Liu ◽  
Ting Shi ◽  
Kendall N. Houk ◽  
Yi-Lei Zhao
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Dna Methyltransferase ◽  
De Novo ◽  
Human Beings ◽  
Epigenetic Methylation ◽  
Key Enzyme ◽  
Dynamics Simulations

The AML-related high-frequent R882H mutation of DNA (cytosine-5)-methyltransferase 3A (DNMT3A), a key enzyme for de novo epigenetic methylation in human beings, was characterized by a disturbing conformation of S-adenosylmethionine (SAM).

Characterization of de novo four-helix bundles by molecular dynamics simulations

2006 ◽  
Vol 64 (3) ◽  
pp. 719-729 ◽  
Author(s):  
Walter R. P. Scott ◽  
Emily Seo ◽  
Heidi Huttunen ◽  
Diana Wallhorn ◽  
John C. Sherman ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
De Novo ◽  
Dynamics Simulations

scholarly journals Accelerating the Discovery of the Beyond Rule of Five Compounds That Have High Affinities Toward SARS-CoV-2 Spike RBD

2021 ◽  
Author(s):  
Abd Al-Aziz Abu-Saleh ◽  
Arpita Yadav ◽  
Raymond A. Poirier
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Rational Design ◽  
De Novo ◽  
Focal Point ◽  
Docking Studies ◽  
Global Pandemic ◽  
Approved Drugs ◽  
Dynamics Simulations ◽  
Binding Energy Calculations

The battle against SARS-CoV-2 coronavirus is the focal point for the global pandemic that has affected millions of lives worldwide. The need for effective and selective therapeutics for the treatment of the disease caused by SARS-CoV-2 is critical. Herein, we performed computational de novo design incorporating molecular docking studies, molecular dynamics simulations, absolute binding energy calculations, and steered molecular dynamics simulations for the discovery of potential compounds with high affinity towards SARS-CoV-2 spike RBD. By leveraging ZINC15 database, a total of 1282 in-clinical and FDA approved drugs were filtered out from nearly 0.5 million protomers of relatively large compounds (MW > 500, and LogP ≤ 5). Our results depict plausible mechanistic aspects related to the blockage of SARS-CoV-2 spike RBD by the top hits discovered. We found that the most promising candidates, namely, ZINC95628821, ZINC95617623, and ZINC261494658, strongly bind to the spike RBD and interfere with the human ACE2 receptor. These findings accelerate the rational design of selective inhibitors targeting the spike RBD protein of SARS-CoV-2.

Assessing protein conformational sampling and structural stability via de novo design and molecular dynamics simulations

Biopolymers ◽  
2015 ◽  
Vol 103 (6) ◽  
pp. 351-361 ◽  
Author(s):  
Keila C. Cunha ◽  
Victor H. Rusu ◽  
Isabelle F. T. Viana ◽  
Ernesto T. A. Marques ◽  
Rafael Dhalia ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Structural Stability ◽  
De Novo ◽  
De Novo Design ◽  
Conformational Sampling ◽  
Dynamics Simulations

scholarly journals Accelerating the Discovery of the Beyond Rule of Five Compounds That Have High Affinities Toward SARS-CoV-2 Spike RBD

2021 ◽  
Author(s):  
Abd Al-Aziz Abu-Saleh ◽  
Arpita Yadav ◽  
Raymond A. Poirier
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Rational Design ◽  
De Novo ◽  
Focal Point ◽  
Docking Studies ◽  
Global Pandemic ◽  
Approved Drugs ◽  
Dynamics Simulations ◽  
Binding Energy Calculations

<div><div><div><p>The battle against SARS-CoV-2 coronavirus is the focal point for the global pandemic that has affected millions of lives worldwide. The need for effective and selective therapeutics for the treatment of the disease caused by SARS-CoV-2 is critical. Herein, we performed computational de novo design incorporating molecular docking studies, molecular dynamics simulations, absolute binding energy calculations, and steered molecular dynamics simulations for the discovery of potential compounds with high affinity towards SARS-CoV-2 spike RBD. By leveraging ZINC15 database, a total of 1282 in-clinical and FDA approved drugs were filtered out from nearly 0.5 million protomers of relatively large compounds (MW > 500, and LogP ≤ 5). Our results depict plausible mechanistic aspects related to the blockage of SARS-CoV-2 spike RBD by the top hits discovered. We found that the most promising candidates, namely, ZINC95628821, ZINC95617623, ZINC3979524, and ZINC261494658, strongly bind to the spike RBD and interfere with the human ACE2 receptor. These findings accelerate the rational design of selective inhibitors targeting the spike RBD protein of SARS-CoV-2.</p></div></div></div>

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