Analyzing a potential drug target N-myristoyltransferase of Plasmodium falciparum through in silico approaches

Abstract

Background:Despite concerted global efforts to combat malaria, malaria elimination is still a remote dream. Fast evolution rate of malarial parasite along with its ability to respond quickly to any drug resulting in partial or complete resistance has been a cause of concern among researcher communities.Materials and Methods:Molecular modeling approach was adopted to gain insight about the structure and various analyses were performed. Modeller 9v3, Protparam, Protscale, MEME, NAMD and other tools were employed for this study. PROCHECK and other tools were used for stereo-chemical quality evaluation.Results and Conclusion:It was observed during the course of study that this protein contains 32.2% of aliphatic amino acids among which Leucine (9.5%) is predominant. Theoretical pI of 8.39 identified the protein as basic in nature and most of the amino acids present in N-Myristoyltransferase are hydrophobic (46.1%). Secondary structure analysis shows predominance of alpha helices and random coils. Motif analyses revealed that this target protein contains 2 signature motifs, i.e., EVNFLCVHK and KFGEGDG. Apart from motif search, three-dimensional model was generated and validated and the stereo-chemical quality check confirmed that 97.7% amino acid residues fall in the core region of Ramachandran plot. Molecular dynamics simulation resulted in maximum 1.3 Å Root Mean Square Deviation (RMSD) between the initial structure and the trajectories obtained later on. The template and the target molecule has shown 1.5 Å RMSD for the C alpha trace. A docking study was also conducted with various ligand molecules among which specific benzofuran compounds turned out to be effective. This derived information will help in designing new inhibitor molecules for this target protein as well in better understanding the parasite protein.

Blunt Snout Bream (Megalobrama amblycephala) MyD88 and TRAF6: Characterisation, Comparative Homology Modelling and Expression

“…As protein structure often reflects its functions [ 40 ], physicochemical analysis and prediction of protein structures can provide basic insights into the functions of proteins at the molecular level. In theory, secondary protein structure is directly related to the hydrogen bonding of α-helix and β-sheet, while random coils usually indicate the absence of a regular secondary structure [ 41 ].…”

Artificial Intelligence in Biological Data

“…Medical informatics, the application of Information Technology techniques involves examination of patient records and reports and through analysing of huge amounts of such data; complex interactions and correlation in it is revealed [42][43][44][45][46]. Practical application is observed in areas such as oncology, liver pathology, thyroid disease diagnosis, rheumatology, dermatology, cardiology, neuropsychology, gynaecology and perinatology [47][48][49][50]. Medical data is now facing serious setbacks as we still have not been able to come up with statistical methods capable of dealing with noisy and missing data [51][52][53].…”