Počet záznamů: 1

An all-atom, active site exploration of antiviral drugs that target Flaviviridae polymerases

SYSNO ASEP	0468801
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	An all-atom, active site exploration of antiviral drugs that target Flaviviridae polymerases
Tvůrce(i)	Valdés, James J. (BC-A)_{RID, ORCID} Gil, V.A. (ES) Butterill, Philip T. (BC-A)_{RID, ORCID} Růžek, Daniel (BC-A)_{RID, ORCID}
Celkový počet autorů	4
Zdroj.dok.	Journal of General Virology. - : Microbiology Society - ISSN 0022-1317 Roč. 97, OCT (2016), s. 2552-2565
Poč.str.	14 s.
Forma vydání	Tištěná - P
Jazyk dok.	eng - angličtina
Země vyd.	GB - Velká Británie
Klíč. slova	dependent RNA-polymerase ; c virus polymerase ; de-novo initiation ; hepatitis C ; allosteric inhibitors ; nucleoside inhibitors ; molecular dynamics ; encephalitis virus ; protein-structure ; cluster-analysis
Vědní obor RIV	EE - Mikrobiologie, virologie
CEP	EE2.3.30.0032 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
	GB14-36098G GA ČR - Grantová agentura ČR
	NV16-34238A GA MZd - Ministerstvo zdravotnictví
Institucionální podpora	BC-A - RVO:60077344
UT WOS	000386872100009
EID SCOPUS	84991609152
DOI	10.1099/jgv.0.000569
Anotace	Natural 2'-modified nucleosides are the most widely used antiviral therapy. In their triphosphorylated form, also known as nucleotide analogues, they target the active site of viral polymerases. Viral polymerases have an overall right-handed structure that includes the palm, fingers and thumb domains. These domains are further subdivided into structurally conserved motifs A-G, common to all viral polymerases. The structural motifs encapsulate the allosteric/initiation (N1) and orthosteric/catalytic (N2) nucleotide-binding sites. The current study investigated how nucleotide analogues explore the N2 site of viral polymerases from three genera of the family Flaviviridae using a stochastic, biophysical, Metropolis Monte Carlo-based software. The biophysical simulations showed a statistical distinction in nucleotide-binding energy and exploration between phylogenetically related viral polymerases. This distinction is clearly demonstrated by the respective analogue contacts made with conserved viral polymerase residues, the heterogeneous dynamics of structural motifs, and the orientation of the nucleotide analogues within the N2 site. Being able to simulate what occurs within viral-polymerase-binding sites can prove useful in rational drug designs against viruses.
Pracoviště	Biologické centrum (od r. 2006)
Kontakt	Dana Hypšová, eje@eje.cz, Tel.: 387 775 214
Rok sběru	2017

Počet záznamů: 1