In silico characterization and molecular dynamics simulation of Pfcyc-1, a cyclin homolog of Plasmodium falciparum

Malaria is still one of the deadly diseases resulting in deaths of millions of people worldwide and situation has become worse due to alarming rise in anti-malarial drug resistance. Genome sequence availability of Plasmodium falciparum, the main causal organism of severe malaria in humans, has enabled identification of various parasite cell cycle regulators like several cyclins and cyclin dependent kinases or CDKs which are promising novel drug targets for Malaria. Here, we present in silico characterization of tertiary structure of Pfcyc-1, a P. falciparum cyclin homolog, which enables identification of key structural elements that contribute to its tertiary structure and function. We have investigated the structure and dynamics of Pfcyc-1 structural model by performing 10 ns molecular dynamics (MD) simulation. Our study indicates that despite poor sequence similarities with cyclin H and A, the characteristic structural cyclin domains are conserved in Pfcyc-1 too. The Pfcyc-1 model reveals a cyclin box, consisting of two tandemly repeating five-helix bundles separated by a linker hinge peptide. Furthermore, the amino acid residues in other known cyclins mediating cyclin-CDK interactions are conserved in Pfcyc-1. The model and its MD simulation offer a first ever structural annotation of any plasmodium cyclin, which along with sequence comparisons, helps in identification of important functional residues mediating the Pfcyc-1-CDK like interactions.