In Silico Analysis of the Structural and Functional Consequences of Polymorphic Amino Acid Substitutions in the Cattle HSF1 Protein

Heat stress causes a decrease in the productivity of livestock by negatively affecting some important economic features such as fertility, growth and milk production. The heat shock transcription factor 1 (HSF1) gene plays a key role in the regulation of the stress response. Therefore, the present study aimed to predict the most deleterious non-synonymous single nucleotide polymorphisms (nsSNP) on the cattle HSF1 gene via in silico analyses. Out of 170 nsSNPs in the HSF1 gene, 14 SNPs were predicted as deleterious by all the nine servers (PredictSNP, Mapp, PhDSNP, PolyPhen-1, PolyPhen-2, Sift, Snap, nsSNPAnalyzer, and Panther). Consurf analysis determined that the vast majority of SNPs predicted to be deleterious were evolutionary conserved. Protein structural analyses were performed I-Mutant, Mupro, Hope Project server, RaptorX and Swiss Model server. The 12 amino acid substitutions (V15G, F18L, L19R, K21M, I35T, V46E, V56G, F61L, A67D, Y76D, V81G, L112P) in the DNA binding region of the cattle HSF1 protein were predicted to be highly deleterious. The P112 variant was predicted to disrupt an a-helix structure. It was determined that the two amino acid changes (K21M, Y76D) on the surface of the protein were different in terms of hydrophobicity, charge, and size. These variants (M21, D76) might hamper the protein's interaction with the heat shock elements.