Programme

P.25 -- Poster, VCTP-46

Date: Tuesday, 5 October 2021

Time: 08:30 - 10:00

Investigate ALP binding mechanism to allele HLA-A*33:03 using Molecular Dynamic simulation

Oanh Phuong Pham (1), Hien T. T. Lai (1), Toan T. Nguyen (1)

(1) VNU Key Laboratory Multiscale Simulation of Complex Systems VNU University of Science, Vietnam National University, Hanoi 334 Nguyen Trai Street, Thanh Xuan, Hanoi 11416, Vietnam 

Allopurinol (ALP), a xanthine oxidase inhibitor, is a urate-lowering medication that is FDA approved for the management of gout, prevention of tumor lysis syndrome, and prevention of recurrent calcium nephrolithiasis in patients with hyperuricosuria, has been reported as a common cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), HSS/DRESS. Some reports proved that allopurinol-induced SCAR has a strong association with HLA-B*5801 that was observed in Han Chinese, Korean and Thai populations with high frequency, while low frequency to European, Japanese. However, as reports by the Bach Mai hospital, although patients do not have the HLA-B*5801 allele, they still had allopurinol-induced SCAR. Very interesting these patients have high frequency with HLA-A*3303 allele (occurred in 10 of 23, 43.5%). So, in this research, we study the effects of ALP on the HLA-A*3303 structure using Molecular Dynamics (MD) simulation methods with three independent replicas. Our results show that all systems HLA-A*3303-ALP are stabled after 100ns simulation time. At the molecular scale, some residues of HLA-A*3303, Val76, Leu81, Ile95, Tyr123 have functions keeping stably its structure in whole simulation and binding to ALP. In addition, ALP has strong interactions with three important residues lived in the active site of HLA-A*3303, containing Asp77, Gln96, Asp116. So, this compound has high binding energy with this allele. From these results, we suggest Asian patients should test alleles HLA-B*5081 as well as HLA-A*3303 before using Allopurinol to avoid drug side effects.

Presenter: Tran Ba Duong