Specific interactions between zinc metalloproteinase and its inhibitors: Ab initio fragment molecular orbital calculations

Ara, Ayami; Kadoya, Ryushi; Ishimura, Hiromi; Shimamura, Kanako; Sylte, Ingebrigt; Kurita, Noriyuki

doi:10.1016/j.jmgm.2017.05.013

Cited by 6 publications

(3 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A possible overlap of coronaviral papain-like proteases with substrate specificities of host deubiquitylating enzymes makes it difficult to design active-site inhibitors. Highly specific active-site inhibitors are therefore desired [ 250 ]. Allosteric modulators and other compounds with alternative mechanisms of action could be more suitable to avoid off-target binding.…”

Section: Rna Virusesmentioning

confidence: 99%

Precursors of Viral Proteases as Distinct Drug Targets

Majerová

Novotny

2021

Viruses

View full text Add to dashboard Cite

Viral proteases are indispensable for successful virion maturation, thus making them a prominent drug target. Their enzyme activity is tightly spatiotemporally regulated by expression in the precursor form with little or no activity, followed by activation via autoprocessing. These cleavage events are frequently triggered upon transportation to a specific compartment inside the host cell. Typically, precursor oligomerization or the presence of a co-factor is needed for activation. A detailed understanding of these mechanisms will allow ligands with non-canonical mechanisms of action to be designed, which would specifically modulate the initial irreversible steps of viral protease autoactivation. Binding sites exclusive to the precursor, including binding sites beyond the protease domain, can be exploited. Both inhibition and up-regulation of the proteolytic activity of viral proteases can be detrimental for the virus. All these possibilities are discussed using examples of medically relevant viruses including herpesviruses, adenoviruses, retroviruses, picornaviruses, caliciviruses, togaviruses, flaviviruses, and coronaviruses.

show abstract

Section: Rna Virusesmentioning

confidence: 99%

Precursors of Viral Proteases as Distinct Drug Targets

Majerová

Novotny

2021

Viruses

View full text Add to dashboard Cite

show abstract

“…Another approach would be use of multiple snapshots generated by MM-MD to include thermal fluctuations of the structures and physical properties [10,14,15,28,29, and so on]. We do not deny the advantage of the latter approach, but this time we took the former approach because the main purpose was to determine the solvation effect on the solutes whose structures were not too deviated from the experimental ones.…”

Section: Preparation Of the Molecular Structures For Fmomentioning

confidence: 99%

“…However, it is more realistic to use an explicit solvent model. Hence, FMO calculations have been performed with explicit models for an oligopeptide [8], proteins [9][10][11], ligands [12], protein/ligand complexes [13][14][15], double-stranded (ds) DNAs [16,17], and a protein/dsDNA complex [18]. To the list we would like to add a single-stranded DNA (ssDNA) and its complex with a protein.…”

Section: Introductionmentioning

confidence: 99%

Explicit solvation of a single-stranded DNA, a binding protein, and their complex: a suitable protocol for fragment molecular orbital calculation

Komeij

Okiyama²,

Mochizuki

et al. 2017

CBIJ

View full text Add to dashboard Cite

Fragment molecular orbital (FMO) calculations were performed for explicitly solvated single-stranded DNA (ssDNA), ssDNA binding protein, and their complex in order to assess the solvent effects on the solutes and thereby to find optimal solvation conditions for FMO calculation. A series of solvated structures were generated with different solvent thicknesses. The structures were subjected to FMO calculation at MP2/6-31G* to obtain the net charges and internal energies of the solutes and the solute-solvent interaction energies as functions of the solvent thickness. In all cases, the properties showed complete or marginal convergence at ca. 6 Ǻ, regardless whether or not the system charge was neutralized. This suggested that the first and second solvent shells mainly determine the electronic structure of a solute while the outer solvent including ions has only minor effects, consistent with several preceding reports. In light of this, and considering safety as a factor, we conclude that a solvent shell thickness of ca. 8 Ǻ suffices for FMO calculation of the solutes.

show abstract

FMO Interfaced with Molecular Dynamics Simulation

Komeiji¹,

Ishikawa

2021

Recent Advances of the Fragment Molecular Orbital Method

View full text Add to dashboard Cite

Specific interactions between zinc metalloproteinase and its inhibitors: Ab initio fragment molecular orbital calculations

Cited by 6 publications

References 19 publications

Precursors of Viral Proteases as Distinct Drug Targets

Precursors of Viral Proteases as Distinct Drug Targets

Explicit solvation of a single-stranded DNA, a binding protein, and their complex: a suitable protocol for fragment molecular orbital calculation

FMO Interfaced with Molecular Dynamics Simulation

Contact Info

Product

Resources

About