D224V and S128Y mutation in FSHR ED influence thumb movement differentially: An intricate insight gained by short‐term molecular dynamics simulation

D224V and S128Y mutation in FSHR ED influence thumb movement differentially: An intricate insight gained by short‐term molecular dynamics simulation Fatemeh Rahimi Gharemirshamlu Department of Genetics, College of Science, Kazerun Branch Islamic Azad University Kāzerūn Iran Maliha Afsar Department of Pathology Osmania General Hospital Hyderabad India Taseem A. Mokhdomi Division of Animal Health Computational Lab, Daskdān Biotech Solutions Ltd Srinagar India http://orcid.org/0000-0001-8903-9662 Asif Amin Department of Biotechnology University of Kashmir Srinagar Jammu and Kashmir India Shoiab Bukhari Division of Animal Health Computational Lab, Daskdān Biotech Solutions Ltd Srinagar India Anbarasu Krishnan Department of Bioinformatics School of Life Sciences, Vels University Chennai India Chundi Vinay Kumar Department of Biological Sciences Brock University St. Catharines Ontario Canada Kourosh Bamdad Department of Biology Payame Noor University Iran Trupti N. Patel Department of Medical Biotechnology, School of Bioscience and Technology, VIT University Vellore India Raies A. Qadri Department of Biotechnology University of Kashmir Srinagar Jammu and Kashmir India Naveed Anjum Chikan Division of Animal Health Computational Lab, Daskdān Biotech Solutions Ltd Srinagar India http://orcid.org/0000-0002-5977-0531 Nadeem Shabir Division of Animal Biotechnology Faculty of Veterinary Sciences & Animal Husbandry, SKUAST‐Kashmir, Shuhama Srinagar Jammu and Kashmir India http://orcid.org/0000-0001-6358-5251 Abstract

Follicle‐stimulating hormone‐follicle‐stimulating hormone receptor (FSH‐FSHR) interaction is one of the most thoroughly studied signaling pathways primarily because of being implicated in sexual reproduction in mammals by way of maintaining gonadal function and sexual fertility. Despite material advances in understanding the role of point mutations, their mechanistic basis in FSH‐FSHR signaling is still confined to mystically altered behavior of sTYS335 (sulfated tyrosine) yet lacking a substantial theory. To understand the structural basis of receptor modulation, we choose two behaviorally contradicting mutations, namely S128Y (activating) and D224Y (inactivating), found in FSH receptor responsible for ovarian hyperstimulation syndrome and ovarian dysgenesis , respectively. Using short‐term molecular dynamics simulations, the atomic scale investigations reveal that the binding pattern of sTYS with FSH and movement of the thumb region of FSHR show distinct contrasting patterns in the two mutants, which supposedly could be a critical factor for differential FSHR behavior in activating and inactivating mutations.
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