Biophysical Society Thematic Meeting

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts

30-POS

Board 30

Homology Modelling of Trypanosoma Cathepsin B like Proteases as a Prelude to Enhibitor

Docking Studies

Mokhawa Mokhawa

1,2

, Kevin A. Lobb

, Ozlem T. Bishop

Rhodes University, Grahamstown, Eastern Cape, South Africa.

Rhodes University,

Grahamstown, Eastern Cape, South Africa,

Trypanosoma brucei (T. brucei) is a protozoan parasite that causes Human African

Trypanosomiasis (HAT), a fatal disease if left untreated. Parasite resistance to drugs and drug

toxicity necessitates the need for novel methods. This study aims to use bioinformatics

approaches to carry out comparative sequence and structural analysis of Trypanosoma brucei

cathepsin B-like (TbCatB) protease and its homologs from T. congolense, T, cruzi, T. vivax and

H. sapiens as a prelude to docking studies. TbCatB is a papain family C1 cysteine protease which

belongs to Clan CA group and has emerged as a potential HAT drug target. Sequences of

TbCatB (PDB ID 3HHI) homologs were retrieved by a BLAST search. Human cathepsin B

(PDB ID: 3CBJ) was selected from a list of templates for homology modelling found by

HHpred. MODELLER version 9.10 program was used to generate a hundred models for T.

congolense, T, cruzi and T. vivax cathepsin B like proteases using 3HHI and 3CBJ as templates.

The best models were chosen based on their DOPE Z scores before validation using

MetaMQAPII, ANOLEA, PROCHECK and QMEAN6. The DOPE Z scores of the models were

-1.02, -0.55, and -1.39 while PROCHECK results indicate that 99.9%, 99.4% and 100 % of

residues are in allowed regions for T. congolense, T. cruzi and T. vivax cathepsin B like protease

models respectively. Evaluation of the models indicate the models are stable and of good quality.

Screening of South African natural compounds identified compounds with good binding energies

in TbCatB, simultaneously having poor binding in human Cathepsin B (with estimated

difference in binding of more than1.0 kcal/mol)