# Identification of Some Glutamic Acid Derivatives with Biological Potential by Computational Methods
## 2 Results and Discussion
### Characterisation of the \"Lead\" Compounds
Before the actual dynamics simulation, the chemical structure was processed according to the protocol established in the literature: hydrogen atoms were inserted, the protonation status corresponding to glutamic acid was used, and Gasteiger partial charges were assigned. The study was performed in water as solvent (SPCBOX, cube size 3 A) with a density of 1024 g/cm\({}^{3}\) to simulate physiological conditions. In the neutralisation phase, we added Na/Cl counterions. The next step was the minimisation phase, whereby the system's energy would tend towards 0. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**No.** & **ID Code** & **Rat IP LD50 (mg/kg)** & **Rat IV LD50 (mg/kg)** & **Rat Oral LD50 (mg/kg)** & **Rat SC LD50 (mg/kg)** \\ \hline
1 & 1 Aa7 & 2593.000 in AD & 1256.000 in AD & 5859.000 in AD & 6254.000 in AD \\
2 & 1 Aa8 & 3059.000 in AD & 1268.000 in AD & 4228.000 in AD & 4014.000 in AD \\
3 & 2 Ba2 & 1069.000 in AD & 1017.000 in AD & 1978.000 in AD & 1027.000 in AD \\
4 & 2 Ba5 & 436.000 in AD & 865.000 in AD & 1861.000 in AD & 1026.000 out of AD \\
5 & 2 Ba6 & 375.200 in AD & 613.100 in AD & 1198.000 in AD & 505.500 in AD \\
6 & 3 Aa3 & 418.900 in AD & 643.600 in AD & 3172.000 in AD & 2290.000 in AD \\
7 & 3 Aa5 & 585.600 in AD & 464.800 in AD & 2623.000 out of AD & 1923.000 in AD \\
8 & 4 Da11 & 551.700 out of AD & 580.800 in AD & 3362.000 in AD & 298.500 in AD \\
9 & 4 Db6 & 298.100 out of AD & 180.400 in AD & 1456.000 out of AD & 76.460 in AD \\ \hline \hline \end{tabular}
\end{table} 
Table 10: Acute toxicity in rodents when administered intraperitoneally, intravenously, orally, and subcutaneously: LD50 in mg/kg [138]. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline \multirow{2}{*}{**No.**} & \multirow{2}{*}{**ID Code**} & \multicolumn{3}{c}{**Mechanism of Action**} & \multicolumn{3}{c}{**Toxic Effects**} \\ \cline{3-6}  & & **Pa** & **Pi** & **Activity** & **Pa** & **Pi** & **Activity** \\ \hline \multirow{8}{*}{7} & \multirow{8}{*}{3 Aa5} & 0.797 & 0.014 & Acylcarnitinehe hydrolase & \multirow{8}{*}{0.764} & \multirow{8}{*}{0.022} & \multirow{8}{*}{Stomatitis} \\  & & 0.787 & 0.005 & & & \\  & & 0.794 & 0.019 & & & \\  & & 0.734 & 0.002 & & & \\  & & 0.736 & 0.021 & & & \\  & & 0.736 & 0.021 & & & \\ \hline \multirow{8}{*}{8} & \multirow{8}{*}{4 Da11} & 0.932 & 0.004 & Angiogenesis inhibitor & 0.496 & 0.074 & Haematemesis \\  & & 0.930 & 0.004 & Anti-inflammatory & 0.439 & 0.038 & Thrombocytopoiesis \\  & & 0.923 & 0.004 & & & & inhibitor \\  & & 0.869 & 0.001 & & & \\  & & 0.865 & 0.002 & & & \\ \hline \multirow{8}{*}{9} & \multirow{8}{*}{4 Db6} & 0.957 & 0.002 & Glutamate-5-semialdehyde & \multirow{8}{*}{0.436} & \multirow{8}{*}{0.078} & \multirow{8}{*}{Interstitial nephritis} \\  & & 0.952 & 0.000 & & & & \\  & & 0.793 & 0.002 & & & \\ \cline{1-1}  & & 0.793 & 0.002 & & & \\ \cline{1-1}  & & 0.782 & 0.003 & & & \\ \cline{1-1}  & & 0.701 & 0.003 & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 9: _Cont._In the equilibration phase, the temperature was set to 310 K (36.85 \({}^{0}\)C, approximately physiological temperature) with a gradient of 10 K/ps. In the production phase, the following settings were made: Andersen barostat--pressure 1.0132 bar, relaxation time 1.5; Nose thermostat--temperature 310 K, relaxation time: 0.2. The entire simulation time was set to 100 ns. The energy values resulting from the molecular dynamics simulation for compound 4 Db6 are included in Table 12.  
Geometry optimisation was performed following the Gaussian model, and we used the standard topology for non-protein molecules. Most biological processes involve, at the atomic scale, the recognition of one molecule by another. Estimation of such interactions at the molecular level is performed by docking methods [146]. In the molecular docking study, the interaction of the 4 Db6 derivative with the GS enzyme was evaluated in comparison with phosphinothricin ((2S)-2-amino-4-(hydroxy-methyl-phosphor))butanoic acid), whose PDB code is PPQ [67; 69; 70; 142; 147].