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Molecular dynamics simulation and docking studies on novel mutants (T11V, T12P and D364S) of the nucleotide-binding domain of human heat shock 70 kDa protein

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Abstract

The aim of investigating protein interaction between Homo sapiens adenovirus and heat shock 70 kDa protein (Hsp70) is to study a potentially synergistic interaction that would enhance the anti-apoptotic mechanisms, hence increasing the virus replication rate and improve the killing efficiency of tumour cells in cancer therapy. Currently, the protein interaction between Hsp70 and E1A 32 kDa of human adenovirus C serotype 5 (Ad5) is still unknown. Mutant models (T11V, T12P and D364S) were built, simulated and their interactions with Ad5 were studied. The E1A 32 kDa of human Ad5 motif (PNLVP) showed the lowest binding energy and intermolecular energy values with the novel T11V mutant at −8.26 kcal/mol and −11.21 kcal/mol. The protein-ligand complex models revealed that the T11V mutant had the strongest and most stable interaction with the PNLVP motif among all the four protein-ligand complex structures. This knowledge would assist future in vivo investigations of this protein-ligand complex structure in cancer treatment research.

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Abbreviations

Ad5:

adenovirus C serotype 5

GRAVY:

grand average of hydropathicity

HLS:

helical lid subdomain

Hsp:

heat shock protein

Hsp70:

heat shock 70 kDa protein

MD:

molecular dynamics

NBD:

nucleotide-binding domain

RMSD:

root mean square deviation

RMSF:

root mean square fluctuation

SASA:

solvent accessible surface area

SBD:

substrate-binding domain

SBSD:

substrate-binding subdomain

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  1. Department of Biosciences and Health Sciences, Faculty of Biosciences and Medical Engineering, Universiti Teknologi Malaysia, 81310, Skudai, Malaysia

    Asita Elengoe, Mohammed Abu Naser & Salehhuddin Hamdan

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  1. Asita Elengoe
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  2. Mohammed Abu Naser
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  3. Salehhuddin Hamdan
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Correspondence to Salehhuddin Hamdan.

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Elengoe, A., Naser, M.A. & Hamdan, S. Molecular dynamics simulation and docking studies on novel mutants (T11V, T12P and D364S) of the nucleotide-binding domain of human heat shock 70 kDa protein. Biologia 70, 1655–1671 (2015). https://doi.org/10.1515/biolog-2015-0194

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