Table 2.
In-silico analysis of physicochemical and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties of 13-amino acid peptide inhibitor (13AApi) from ExPasy ProtParam (ExPASy—ProtParam tool) and pkCSM (pkCSM [unimelb.edu.au]) tools
| Peptide sequence | FLDKFNHNFKDLF |
|---|---|
| Physicochemical analysis | |
| Properties | |
| Molecular weight (g/mol) | 1684.91 |
| Theoretical pI | 7.55 |
| Net charge at pH 7 | 0.1 |
| Negative + positive residues | 2 +2 |
| Molecular formula | C82H113N19O20 |
| Number of atoms | 234 |
| Instability Index | − 2.21 |
| Half-life (in h) | 1.1 |
| Hydrophobicity (%) | 46.15 |
| Acidic + Basic + neutral ratio (%) | 15.38 + 23.08 + 15.38 |
| GRAVY | − 0.477 |
| ADMET analysis | |
| Absorption | |
| Water solubility (log mol/L)_ | − 2.892 |
| Skin perm (log Kp) | − 2.735 |
| Distribution | |
| Fraction unbound (human) (Fu) | 0.369 |
| BBB permeability | − 2.493 |
| CNS permeability (logPS) | − 7.089 |
| Metabolism | |
| Cytochrome P substrate | No |
| Cyctochrome P inhibitor | No |
| Excretion | |
| Total clearance (log mL/min/kg) | − 1.052 |
| Toxicity | |
| AMES toxicity | No |
| Skin sensitisation | No |
| MRTD human (log mg/kg/day) | 0.438 |
| Rat oral LD50 (mol/kg) | 2.482 |
For the ADMET analysis in pkCSM, the required SMILES file format of the 13AApi was created using pepSMI tool (PepSMI: Convert Peptide to SMILES string [novoprolabs.com])
BBB Permeability logBB < − 1 indicates poor distribution to the brain, CNS permeability logPS > − 2 classifies central nervous system penetration and logPS < − 3 classifies no central nervous system penetration, Fraction Unbound defines amount that remains unbound to plasma protein for pharmacological action, GRAVY Grand Average of Hydropathy, Instability Index value below 40 classifies stable protein/peptide, MRTD maximum recommended tolerated dose (should be less than 0.477 mg/kg/day), pI isoelectric point, Skin Perm logkp > − 2.5 classifies low skin permeability, Total Clearance includes both hepatic and renal clearance, Water Solubility logS defines solubility in water at 25 °C