Dataset on anti-human insulin-degrading enzyme activities of cyclic tetra peptides: Insight from insilico approach

In this work, the biochemical activities of seven cyclic peptides were investigated using the insilico approach. The materials used in this work were Spartan 14 for quantum chemical analysis, molecular operating environment software for molecular docking and ADMETSAR 2.0 for pharmacokinetic investigation. The calculated features obtained for each compound were explored and it was observed that the molecules used in this research have potential anti-human insulin-degrading enzyme activities. Also, (3S,6S,9S)-9-((R)-1-(benzyloxy)ethyl)-6-methyl-3-(4-methylphenethyl)-1,4,7,10-tetraazacyclododecane-2,5,8,11-tetraone (compound 2) with highest binding affinity (−7.95349026 kcal/mol) possess utmost ability to inhibit human insulin-degrading enzyme (PDB id: 2g56) than other investigated compounds and acarbose (referenced compound). The pharmacokinetic analysis for compound 2 was examined and compared to the predicted report for the referenced compound.

In this work, the biochemical activities of seven cyclic peptides were investigated using the insilico approach.The materials used in this work were Spartan 14 for quantum chemical analysis, molecular operating environment software for molecular docking and ADMETSAR 2.0 for pharmacokinetic investigation.The calculated features obtained for each compound were explored and it was observed that the molecules used in this research have potential anti-human insulin-degrading enzyme activities.Also, (3S,6S,9S)-9-(( R )-1-(benzyloxy)ethyl)-6-methyl-3-(4-methylphenethyl)-1,4,7,10-tetraazacyclododecane-2,5,8,11-tetraone (compound 2) with highest binding affinity (−7.95349026 kcal/mol) possess utmost ability to inhibit human insulin-degrading enzyme (PDB id: 2g56) than other investigated compounds and acarbose (referenced compound).The pharmacokinetic analysis for compound 2 was examined and compared to the predicted report for the referenced compound.
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Value of the Data
• The obtained descriptors from the optimized compounds in different phases (vacuum, water, and ethanol) will expose to scientists the solvent that is suitable for the solubility of the examined compounds.• The predicted data from the optimized compounds will help scientists to know the level of reactivity of the optimized compounds.• The calculated binding affinity for the investigated compounds against human insulindegrading enzyme (PDB id: 2g56) will reveal to researchers the compound that has the best ability to inhibit the examined receptor.• The predicted binding energy, root mean square deviation (rmsd), root means square fluctuation (rmsf), the radius of gyration (rog) and hydrogen bond calculation will help researchers to confirm compounds with the highest ability to inhibit the human insulin-degrading enzyme (PDB id: 2g56).• The predicted pharmacokinetics will assist researchers in discerning the probable biochemical activities of individual ligands in the human body system.

Background
The objectives of this work are: ➢ To examine the effect of solvent on the reactivity of the investigated cyclic peptides.➢ To observe the biochemical activities of the compounds in the active site of human insulindegrading enzyme (PDB id: 2g56).➢ To reveal the level of toxicity of the lead compound.

Data Description
The structure and IUPAC names of the examined compounds are displayed in Table 1 .Table 1 comprises seven compounds and the parent compound was attached to each of the following atom/molecules: Hydrogen, Methylbenzene, Methylbenzoate, Flourobenze, 3,5dimethylbenzene, Chlorobenzene and Bromobenzene to form individual compound investigated in this work.Table 2 revealed the descriptors which described the activities of the examined compounds and the descriptors obtained from the investigated phases were highest occupied molecular orbital energy (EHOMO), lowest unoccupied molecular orbital energy (ELUMO) and energy gap.
The precise locations for HOMO-LUMO overlay on the compounds under investigation were displayed in Tables 3-5 .The HOMO-LUMO overlay for the compound optimized in vacuum, water and ethanol was represented using solid, mesh and transparent format respectively.

Table 4
Predicted HOMO-LUMO overlay for examined cyclic peptide-based compound in Water Phase.

Table 5
Predicted HOMO-LUMO overlay for examined cyclic peptide-based compound in Ethanol Phase. the amino acid involved in the interaction, the distance and the part of the ligand involved in the interaction were presented in Table 7 and the 2-dimensional structure of the ligand in the active site of the investigated receptor were presented in Figs.1-7 .
Tables 8 and 9 show the pharmacokinetic analysis of the lead (compound 2) and reference compounds.The analysis was presented in ADMET predicted profile -classification and AD-MET predicted profile -regression format.The prediction was displayed under three headings (model, result and probalility) and the predicted model for absorption were Blood-Brain Barrier, Human Intestinal Absorption, Caco-2 Permeability, P-glycoprotein Substrate, P-glycoprotein Inhibitor and Renal Organic Cation Transporter; for distribution was Subcellular localization; metabolism were CYP450 2C9 Substrate, CYP450 2D6 Substrate, CYP450 3A4 Substrate, CYP450 1A2 Inhibitor, CYP450 2C9 Inhibitor, CYP450 2D6 Inhibitor, CYP450 2C19 Inhibitor, CYP450 3A4 Inhibitor and CYP Inhibitory Promiscuity and for toxicity, the Human Ether-a-go-go-Related Gene Inhibition, AMES Toxicity, Carcinogens, Fish Toxicity, Tetrahymena Pyriformis Toxicity, Honey Bee Toxicity, Biodegradation, Acute Oral Toxicity and Carcinogenicity (Three-class) were considered.
Moreover, the factors considered for ADMET predicted profile -regression were Aqueous solubility, Caco-2 Permeability (absorption) and Rat Acute Toxicity, Fish Toxicity and Tetrahymena Pyriformis Toxicity (toxicity).

Experimental Design, Materials and Methods
The investigated cyclic peptide-based compounds were modelled using Spartan '14 software [1][2][3] by linking the appropriate atoms to each other via a bond creation tool.The compounds under investigation were optimized using the density functional theory method via 6-31G * * as basis set and the electronic descriptors obtained were reported accordingly.In this work, the human insulin-degrading enzyme (PDB id: 2g56) [ 4 ] was retrieved from a protein data bank and it was treated and prepared for docking using the induced fit method via molecular operating environment (MOE) software [ 5 , 6 ].The calculated binding affinity for individual cyclic peptides was acquired and presented.
). Published by Elsevier Inc.This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Table 1
Structure and IUPAC names of the Investigated compounds.
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Table 2
Predicted descriptors from the optimized compounds in Gas Phase, water and Ethanol.

Table 6
Calculated binding affinity for Cyclic Peptides based compounds and human insulin-degrading enzyme (PDB id: 2g56).