Title: DNA and protein modeling for P/asmodium falciparum dhfr and dhps sequences derived from an existing study in Kenya

Project Team: Shirley Luckhart, Dharmesh Patel, JT Van Leuven

Start Date: June, 2019

The UI, USUHS, and USAMRU-K teams have collected human blood samples from study-enrolled Kenyan adults for an NIH-funded project focused on defining the impacts of HIV-malaria co-infection and HIV treatment.

We have completed deep sequencing, cleaning and clustering of dhfr and dhps genotypes and have identified frequencies for the dhfr and dhps SNPs known to be associated with sulfadoxine-pyrimethamine drug resistance.

However, given the AT-rich codon bias and mutation frequency of P. falciparum per asexual parasite cycle, we have noted other nucleotide substitutions in our sequences that we would like to explore with modeling.

We seek to classify whether these nucleotide changes are:
(1) substitutions that affect codon frequency but are synonymous,
(2) non-synonymous substitutions that are conservative, and
(3) non-synonymous substitutions that are non-conservative,
all of which could be predicted to alter protein structure or function.