In Silico Docking of HNF-1a Receptor Ligands.

Background. HNF-1a is a transcription factor that regulates glucose metabolism by expression in various tissues. Aim. To dock potential ligands of HNF-1a using docking software in silico. Methods. We performed in silico studies using HNF-1a protein 2GYP·pdb and the following softwares: ISIS/Draw 2.5SP4, ARGUSLAB 4.0.1, and HEX5.1. Observations. The docking distances (in angstrom units: 1 angstrom unit (Å) = 0.1 nanometer or 1 × 10(-10) metres) with ligands in decreasing order are as follows: resveratrol (3.8 Å), aspirin (4.5 Å), stearic acid (4.9 Å), retinol (6.0 Å), nitrazepam (6.8 Å), ibuprofen (7.9 Å), azulfidine (9.0 Å), simvastatin (9.0 Å), elaidic acid (10.1 Å), and oleic acid (11.6 Å). Conclusion. HNF-1a domain interacted most closely with resveratrol and aspirin.

Butyrylcholinesterase in metabolic syndrome.

Butyrylcholinesterase may have a role in a number of metabolic functions and could affect the expression of insulin resistance syndrome. We present our integrated work using clinical, biochemical and bioinformatic approaches to delineate the possible function of this enzyme. Initially, we constructed a phylogenic tree with nucleotides and amino acid sequences and showed the existence of similar sequences in bacteria, plants and in other animals. We also demonstrated a possible pathogenic role for BChE in the common existence of insulin resistance, type 2 diabetes and Alzheimer's disease by in silico method and followed it up with a diabetic mouse study where cognition was slowed along with changes in BChE levels. In the next group of in silico studies, we employed THEMATICS method to identify the amino acids at the active site and later performed docking studies with drugs. THEMATICS predicted two clusters of ionisable amino acid residues that are in proximity: one with two residues and another with 11 showed perturbation in the THEMATICS curves. Using ISIS/Draw 2.5SP4, ARGUSLAB 4.0.1 and HEX 5.1. software. 3-D ligands were docked with BChE motif (from PDB). We did not find any of the ligands studied with significant docking distance, indicating they did not have direct interaction with the active site. Subsequently we performed in silico studies to compare the secondary structure and domain of BChE. Protein-protein interaction showed the following intersections with BChE UBE21, CHAT, APOE, AATF, DF ALDH9A1, PDHX, PONI PSME3 and ATP6VOA2. The integrative physiological roles of proteins with poorly known functions can be approached by generating leads in silico, which can be studied in vivo, setting into movement an iterative process.