BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//CERN//INDICO//EN
BEGIN:VEVENT
SUMMARY:The N-methyl-D-aspartate receptor ligand binding domain and the in
 teractivity with ion-channel control
DTSTART;VALUE=DATE-TIME:20211125T072200Z
DTEND;VALUE=DATE-TIME:20211125T072300Z
DTSTAMP;VALUE=DATE-TIME:20260306T090918Z
UID:indico-contribution-4220@events01.synchrotron.org.au
DESCRIPTION:Speakers: Zheng Chen (The University of Sydney)\nEncephalopath
 ies are a group of brain dysfunctions which leads to cognitive\, sensory\,
  and motor impairments. Recent developments in the field have led to the i
 dentification of several mutations within the N-methyl-D-aspartate recepto
 r as one of the possible culprits for this group of conditions. However\, 
 understanding of the underlying changes to the receptor due to these mutat
 ions has been elusive to date. We aimed to determine the effects of one of
  the first mutations identified within the N-methyl-D-aspartate receptor G
 luN1 ligand binding domain\, Ser688Tyr. This mutation was identified and a
 ssociated with early onset encephalopathy. We performed molecular docking\
 , randomly seeded molecular dynamics simulations\, and binding free energy
  calculations to determine the behaviour of the 2 main co-agonists: glycin
 e and D-serine and their effects on ion channel function. We determined th
 at the Ser688Tyr mutation leads to instability of both ligands within the 
 ligand binding site due to changes within the ligand binding domain associ
 ated with the mutation. Associated binding free energy for both ligands al
 so increased significantly in the mutated receptor. These results reinforc
 e previously observed in vitro electrophysiology data and provides additio
 nal information on ligand behaviour. Upcoming studies involve the use of c
 rystallography and neutron scattering to determine the effects of this mut
 ation on ion-channel function. This study provides valuable insight into t
 he consequences of mutations within the N-methyl-D-aspartate receptor GluN
 1 ligand binding domain.\n\nhttps://events01.synchrotron.org.au/event/146/
 contributions/4220/
LOCATION:Online
URL:https://events01.synchrotron.org.au/event/146/contributions/4220/
END:VEVENT
END:VCALENDAR