Chemical Informatics

In-Silico Assessment of Various PDB Entries of Pfldh Enzyme for their Use in SBDD

Objective: To perform in-silico structural assessment analysis of protein database entries of Plasmodium falciparum lactate dehydrogenase (PfLDH) enzyme, an important target for designing of anti-malarial drugs.

Methods: Seven PDB ID's of the enzyme PfLDH, viz. 1T2D, 1T24, 1U4O, 1U5A, 1XIV, 2A94 and 4B7U were selected and downloaded from Protein Data Bank (PDB). These were subjected to Atomic Non-Local Environment Assessment (ANOLEA) energy assessment analysis and Swiss model was used to analyse Ramachandran plot.

Results: The energy assessment analysis and analysis of Ramachandran plot were carried out successfully. ANOLEA energy assessment displayed that 1T24 has 304 amino acids, only 1 high energy molecule, total non-local energy of -2722 E/Kt units and Non local normalized Z-score of -0.81. All the other PDB ID's had either more than 6 high energy amino acids or more total non-local energy or more non local normalized energy Z-Score than 1T24. Hence, it was inferred that 1T24 might be the best PDB ID amongst all. ANOLEA energy assessment analysis was also used to analyze the high energy amino acid residues of chain A of all the seven PDB’s. The total energy of PDB ID 1T24 (1.149 E/kT units) was found to be lowest and supported the inference that PDB ID 1T24 is better than others. Finally, Ramachandran plot analysis revealed that 1T24 has the highest percentage of residues in the allowed regions and only 0.4% in disallowed region and hence forth the inference was reinforced.

Conclusion: From ANOLEA energy assessment and Ramachandran plot analysis it was concluded that out of all the PDB entries, PBD 1T24 will be the best suit for carrying out structure based drug design (SBDD) studies.

Author(s):

Apeksha Shrivastava, Jintender Kumar, Mymoona Akhter, Mumtaz Alam M and Shaqiquzamman M

Abstract | Full-Text | PDF

Share this