Title:Understanding Interactions between a Potential Antimalarial ‘MAL2-11B’ and its Targets using In Silico Methods
Volume: 24
Issue: 3
Author(s): Komalpreet Kaur Sandhu, Satinder Kaur, Rachna Hora and Prakash Chandra Mishra*
Affiliation:
- Department of Biotechnology, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
Keywords:
Malaria, Plasmodium falciparum, nucleotide binding domain, molecular docking, heat shock proteins, substrate binding domain.
Abstract:
Introduction: The 70 kDa heat shock proteins (Hsp70) are ubiquitous molecules that
play central roles in protein homeostasis. Their nucleotide-binding domains (NBD) are associated
with the J domains of 40 kDa co-chaperone ‘HSP40’ in performing their functions. Interruption
of this interaction significantly impacts the critical ATPase activity of Hsp70s, making them
dysfunctional.
Methods: MAL2-11B is a dihydropyrimidine derivative that blocks Hsp70-Hsp40 interaction
and hence holds the potential to be used as a drug. This Hsp70 inhibitor is a structural analogue
of MAL3-101 that has proven anti-cancer and antiparasitic activity. MAL2-11B is predicted to
have better drug-likeness, solubility, and absorption properties than MAL3-101. In the present
study, we have therefore explored the potential of MAL2-11B as an antimalarial by using in silico
tools.
Results: Molecular docking of MAL2-11B with all Plasmodium falciparum Hsp70 (PfHsp70)
proteins revealed its preferential affinity for two out of four homologs at the nucleotide-binding
site. Detailed analysis of the docked complexes helped us to predict the kind of protein-inhibitor
interactions and specific amino acid residues involved in binding.
Conclusion: After in vitro validation, these data may be used as the groundwork for the design
and development of new inhibitors and drugs against malaria.
