BACKGROUND: Malaria affects 200-300 million individuals per year worldwide. 
Plasmodium falciparum is the causative agent of the most severe and mortal type 
of malaria. The need for new antimalarials comes from the widespread resistance 
to those in current use. New antimalarial targets are required to increase 
chemical diversity and effectiveness of the drugs. The research for such new 
targets and drug chemotypes is aided by structure-based drug design. We present 
a model of the TBP-TFIIB complex from P. falciparum (pfTBP-pfTFIIB) and a 
detailed study of the interactions at the TBP-TFIIB interface.
METHODS: The model was built using standard methodology, optimized energetically 
and evaluated structurally. We carried out an analysis of the interface 
considering its evolution, available experimental data on TBP and TFIIB mutants, 
and the main conserved and non-conserved interactions. To support the 
perspective of using this complex as a new target for rational antimalarial 
design, we present the comparison of the pfTBP-pfTFIIB interface with its human 
homolog.
RESULTS: Despite the high residue conservation at the interface, we identified a 
potential region, composed of species-specific residues that can be used for 
rational antimalarial design.
CONCLUSIONS: Currently there are no antimalarial drugs targeted to stop the 
nuclear transcription process, a vital event for all replication stages of P. 
falciparum. Due to its absolute requirement in transcription initiation, we 
consider the pfTBP-pfTFIIB interface as a new potential target for novel 
antimalarial chemotypes.