1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
Molecular docking study on the LMNA variant (R427C) effect in hypertrophic cardiomyopathy patient
Paper ID : 1238-ICB10
Authors:
Serwa Ghasemi1, Iman Salahshourifar2, Majid Maleki3, Mohammad Mahdavi4, Samira Kalayinia *5
1دانشجوی دکترا دانشگاه آزاد اسلامی واحد علوم تحقیقات تهران
2هیات علمی دانشگاه /ازاد اسلامی واحد علوم تحقیقات
3هیات علمی مرکز قلب و عروق شهید رجایی
4هیات علمی مرکز قلب و عروث شهید رجایی
5هیات علمی مرکز قلب و عروق شهید رجائی
Abstract:
We studied the effect of the LMNA variant (R427C) in the TGF-β pathway in an Iranian family with hypertrophic cardiomyopathy (HCM) by Molecular docking.

LMNA gene encodes lamin A and C (lamin A/C), which are intermediate filament proteins implicating in different cellular processes. Mutant lamin A/C may change TGF-β1 activity in the regulation of cell cycle progression, negatively. Therefore, cell proliferation will be stimulated in the presence of mutant lamins A/C [1, 2].

Molecular docking was performed using HADDOCK Web Server to investigate the binding mode between the normal and mutant forms of lamin A/C and the MAN1[3, 4]. Data visualization and the interactions were checked by PyMOL and LigPlus+, respectively [5, 6].

In homology modeling, the structural alteration in lamin A/C R427C mutant was revealed. Furthermore, molecular docking identified the affinity of lamin A/C and MAN1 interaction has been reduced in presence of R427C, which followed by TGF-β signaling inhibition and Smad pathway reduction through sequestering at the nuclear envelope (NE).

Molecular docking analysis provided useful information of decreased binding affinity between mutant lamin A/C (R427C) and MAN1 in the HCM disease.
Keywords:
Hypertrophic cardiomyopathy; TGF-β signaling pathway; LMNA; Molecular docking
Status : Paper Accepted (Poster Presentation)