In silico structural modeling and quality assessment of Plasmodium knowlesi apical membrane antigen 1 using comparative protein models
https://doi.org/10.47665/tb.39.3.009
- Author:
Haron, F.N.
1
;
Azazi, A.
1
;
Chua, K.H.
2
;
Lim, Y.A.L.
3
;
Lee, P.C.
4
,
5
;
Chew, C.H.
1
Author Information
1. Faculty of Health Sciences, Universiti Sultan Zainal Abidin, 21300 Kuala Nerus, Terengganu, Malaysia
2. Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
3. Department of Parasitology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
4. Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia&
5. Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia
- Publication Type:Journal Article
- Keywords:
Plasmodium knowlesi;
apical membrane antigen 1 (AMA1);
in silico;
three-dimensional (3D) modeling;
model quality assessment
- From:Tropical Biomedicine
2022;39(No.3):394-401
- CountryMalaysia
- Language:English
-
Abstract:
Plasmodium knowlesi is the most common zoonotic parasite associated with human malaria infection
in Malaysia. Apical membrane antigen 1 (AMA1) protein in the parasite plays a critical role in parasite
invasion into host cells. To date, there is no complete three-dimensional ectodomain structure of P.
knowlesi AMA1 (PkAMA1) protein. The knowledge of a protein structure is important to understand
the protein molecular functions. Three in silico servers with respective structure prediction methods
were used in this study, i.e., SWISS-MODEL for homology modeling and Phyre2 for protein threading,
which are template-based modeling, while I-TASSER for template-free ab initio modeling. Two query
sequences were used in the study, i.e., native ectodomain of PkAMA1 strain H protein designated as
PkAMA1-H and a modified PkAMA1 (mPkAMA1) protein sequence in adaptation for Pichia pastoris
expression. The quality of each model was assessed by ProSA-web, QMEAN and SAVES v6.0 (ERRAT,
Verify3D and Ramachandran plot) servers. Generated models were then superimposed with two models
of Plasmodium AMA1 deposited in Protein Data Bank (PDB), i.e., PkAMA1 (4UV6.B) and Plasmodium
vivax AMA1 (PvAMA1, 1W81) protein structures for similarity assessment, quantified by root-meansquare deviation (RMSD) value. SWISS-MODEL, Phyre2 and I-TASSER server generated two, one and
five models, respectively. All models are of good quality according to ProSA-web assessment. Based on
the average values of model quality assessment and superimposition, the models that recorded highest
values for most parameters were selected as best predicted models, i.e., model 2 for both PkAMA1-H
and mPkAMA1 from SWISS-MODEL as well as model 1 of PkAMA1-H and model 3 of mPkAMA1 from
I-TASSER. Template-based method is useful if known template is available, but template-free method
is more suitable if there is no known available template. Generated models can be used as guidance
in further protein study that requires protein structural data, i.e., protein-protein interaction study.
- Full text:8.2022my1354.pdf
