title: Structural and dynamic investigation of bovine folate receptor alpha (FOLR1), and role of ultra-high temperature processing on conformational and thermodynamic characteristics of FOLR1-folate complex.
abstract: The folate receptor alpha (FOLR1) present in milk has widely been studied to investigate the effects of pasteurization, ultra-high temperature (UHT) processing and fermentation on net folate concentration. However, the folate binding mechanism with FOLR1, and effect of temperature on FOLR1-folate complex is poorly explored till now in bovine milk which is a chief resource of folate. Despite of enormous importance of folic acid and the routine intake of bovine milk, folic acid deficiency diseases are common in human race. To understand the folate deficiency in milk after processing, in absence of experimental structure, 3D model of bovine FOLR1 (bvFOLR1) was built followed by 40ns molecular dynamics (MD) simulation. The folate and its derivatives binding sites in bvFOLR1 were anticipated by molecular docking using AutoDock 4.2. Essential MD studies suggested the presence of a longer signal peptide (22 residues) and a short propeptide (7 residues) at the C-terminus that may cleaved during post-translational modification. MD analysis of bvFOLR1-folate complex at 298, 323, 353, 373 and 408K followed by binding energy (BE) calculation showed maximum binding affinity at ∼353K. However, at 373K and UHT (408K), the folate BE is significantly decreased with substantial conformational alteration. Heating at UHT followed by cooling within 298-408K range demoed no structural reformation with temperature reduction, and the folate was displaced from the active site. This study presented the disintegration of folate from bvFOLR1 during high temperature processing and revealed a lower folate concentration in UHT milk and dairy products.
authors.affiliation: Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar, 751001, India; Laboratory of Molecular Biophysics, Institute for Protein Research, Osaka University, Osaka Prefecture, 5650871, Japan. Electronic address: bikash.bioinformatics@gmail.com.
authors.forename: Bikash Ranjan
authors.initials: BR
authors.lastname: Sahoo
authors.affiliation: Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar, 751001, India; Biotechnology Laboratory, Central Inland Fisheries Research Institute, Barrackpore, Kolkata, West Bengal, 700120, India.
authors.forename: Jitendra
authors.initials: J
authors.lastname: Maharana
authors.affiliation: Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar, 751001, India; Animal Genomics Laboratory, Animal Biotechnology Centre, National Dairy Research Institute, Karnal 132001, India.
authors.forename: Mahesh Chandra
authors.initials: MC
authors.lastname: Patra
authors.affiliation: Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar, 751001, India.
authors.forename: Gopal Krushna
authors.initials: GK
authors.lastname: Bhoi
authors.affiliation: Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar, 751001, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Lenka
authors.affiliation: Immunology Frontier Research Centre, Osaka University, Osaka Prefecture, 5650871, Japan.
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Dubey
authors.affiliation: RIKEN Center for Life Science Technologies, Yokohama, 2300045, Japan.
authors.forename: Shubham
authors.initials: S
authors.lastname: Goyal
authors.affiliation: Department of Agricultural Biotechnology, Assam Agricultural University, Jorhat, 785013, Assam, India.
authors.forename: Budheswar
authors.initials: B
authors.lastname: Dehury
authors.affiliation: Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar, 751001, India.
authors.forename: Sukanta Kumar
authors.initials: SK
authors.lastname: Pradhan
mesh_terms: D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D058975:Folate Receptor 1 / Q000737:chemistry* / Q000378:metabolism*; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry; D040681:Structural Homology, Protein; D013696:Temperature; D014584:User-Computer Interface
chemical_list: D058975:Folate Receptor 1; D012997:Solvents; D005492:Folic Acid; D000409:Alanine
keywords: Binding energy; Bovine; FOLR1; Folate; Molecular dynamics; Ultra-high temperature