Identification, characterization, and CADD analysis of Plasmodium DMAP1 reveals it as a potential molecular target for new anti-malarial discovery

Abstract

Developing drug resistance in the malaria parasite is a reason for apprehension compelling the scientific community to focus on identifying new molecular targets that can be exploited for developing new anti-malarial compounds. Despite the availability of the Plasmodium genome, many protein-coding genes in Plasmodium are still not characterized or very less information is available about their functions. DMAP1 protein is known to be essential for growth and plays an important role in maintaining genomic integrity and transcriptional repression in vertebrate organisms. In this study, we have identified a homolog of DMAP1 in P. falciparum. Our sequence and structural analysis showed that although PfDMAP1 possesses a conserved SANT domain, parasite protein displays significant structural dissimilarities from human homolog at full-length protein level as well as within its SANT domain. PPIN analysis of PfDMAP1 revealed it to be vital for parasite and virtual High-throughput screening of various pharmacophore libraries using BIOVIA platform-identified compounds that pass ADMET profiling and showed specific binding with PfDMAP1. Based on MD simulations and protein–ligand interaction studies two best hits were identified that could be novel potent inhibitors of PfDMAP1 protein.

Communicated by Ramaswamy H. Sarma

Keywords:

• DMAP1
• Plasmodium
• malaria
• CADD
• vHTS

Acknowledgments

We thank Shiv Nadar Institution of Eminence (SNIoE) for providing space and resources. University has no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. JK thanks ICMR for the senior research fellowship.

Authors’ contributions

ML performed experiments in the study, investigation, prepared the illustrations, draft writing; JK performed experiments in the study, investigation, prepared the illustrations, draft writing, and editing; AG Conceived, designed, and supervised the study, original draft writing, review, and editing. AG, ML, and JK participated in analyzing the data. All authors approved the final version of the manuscript.

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.