Molecular dynamics-driven drug discovery: leaping forward with confidence

Ganesan, Aravindhan; Coote, Michelle L.; Barakat, Khaled

doi:10.1016/j.drudis.2016.11.001

Cited by 291 publications

(215 citation statements)

References 200 publications

(137 reference statements)

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“…Interestingly, MD simulation assisted in the discovery and development of antiviral drugs . For the first time, a combination of MD refinements of postdocking complexes and ensemble‐based molecular docking has helped to reveal a unique symmetrical binding mode of daclatasvir with hepatitis C virus (HCV) NS5A protein.…”

Section: Introductionmentioning

confidence: 99%

Perspectives towards antiviral drug discovery against Ebola virus

Mirza

Vanmeert

Ali

et al. 2019

Journal of Medical Virology

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Ebola virus disease (EVD), caused by Ebola viruses, resulted in more than 11 500 deaths according to a recent 2018 WHO report. With mortality rates up to 90%, it is nowadays one of the most deadly infectious diseases. However, no Food and Drug Administration‐approved Ebola drugs or vaccines are available yet with the mainstay of therapy being supportive care. The high fatality rate and absence of effective treatment or vaccination make Ebola virus a category‐A biothreat pathogen. Fortunately, a series of investigational countermeasures have been developed to control and prevent this global threat. This review summarizes the recent therapeutic advances and ongoing research progress from research and development to clinical trials in the development of small‐molecule antiviral drugs, small‐interference RNA molecules, phosphorodiamidate morpholino oligomers, full‐length monoclonal antibodies, and vaccines. Moreover, difficulties are highlighted in the search for effective countermeasures against EVD with additional focus on the interplay between available in silico prediction methods and their evidenced potential in antiviral drug discovery.

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Section: Introductionmentioning

confidence: 99%

Perspectives towards antiviral drug discovery against Ebola virus

Mirza

Vanmeert

Ali

et al. 2019

Journal of Medical Virology

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“…Regarding the systems solvation, although there are other models, TIP3P is probably the most used because of the good dynamic and thermodynamic properties that it provides for most force fields (Jorgensen et al, 1983;Ganesan et al, 2017). The solvated model simulates the adsorption conditions in aqueous medium.…”

Section: Resultsmentioning

confidence: 99%

“…It offers not only ways to solve mathematical calculations, but also, and above all, the creation of virtual laboratories in which studies can be carried out very close to reality. Thus, the understanding and observing of a problem can be done reliably and effectively (Meller, 2001;Rangel-Vázquez, 2015;Ganesan et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Computer simulation of benzene, toluene and p-xylene adsorption onto activated carbon

Costa¹,

Lima²,

Filho³

et al. 2017

Afr. J. Biotechnol.

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In this work, the adsorption of benzene, toluene and p-xylene on activated carbon was verified through a computer simulation. A carbon model was used as the work basis. Several steps were completed from the modeling of the carbon structures and pollutants to simulations of molecular dynamics. After analyzing the results, it was found that the groups: ether, lactone and carbonyl (ketone) present in the carbon structure provided acidic character and due to this fact, and the carbon's complex network of micropores, the adsorption became viable. This study corroborates the present understanding on this type of phenomenon.

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“…However, complications may arise when considering toxicity and risk of parasite resistance [3]. The price of discovering and manufacturing drugs can be exorbitant; thus, alternative routes such as computational methods can help circumvent this problem [4]. …”

Section: Introductionmentioning

confidence: 99%

A Comparative Study of the Structural Dynamics of Four Terminal Uridylyl Transferases

Cheng

Demir

Amaro

2017

Genes

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African trypanosomiasis occurs in 36 countries in sub-Saharan Africa with 10,000 reported cases annually. No definitive remedy is currently available and if left untreated, the disease becomes fatal. Structural and biochemical studies of trypanosomal terminal uridylyl transferases (TUTases) demonstrated their functional role in extensive uridylate insertion/deletion of RNA. Trypanosoma brucei RNA Editing TUTase 1 (TbRET1) is involved in guide RNA 3’ end uridylation and maturation, while TbRET2 is responsible for U-insertion at RNA editing sites. Two additional TUTases called TbMEAT1 and TbTUT4 have also been reported to share similar function. TbRET1 and TbRET2 are essential enzymes for the parasite viability making them potential drug targets. For this study, we clustered molecular dynamics (MD) trajectories of four TUTases based on active site shape measured by Pocket Volume Measurer (POVME) program. Among the four TUTases, TbRET1 exhibited the largest average pocket volume, while TbMEAT1’s and TbTUT4’s active sites displayed the most flexibility. A side pocket was also identified within the active site in all TUTases with TbRET1 having the most pronounced. Our results indicate that TbRET1’s larger side pocket can be exploited to achieve selective inhibitor design as FTMap identifies it as a druggable pocket.

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Molecular dynamics-driven drug discovery: leaping forward with confidence

Cited by 291 publications

References 200 publications

Perspectives towards antiviral drug discovery against Ebola virus

Perspectives towards antiviral drug discovery against Ebola virus

Computer simulation of benzene, toluene and p-xylene adsorption onto activated carbon

A Comparative Study of the Structural Dynamics of Four Terminal Uridylyl Transferases

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