Affiliations 

  • 1 Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand; Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
  • 2 Ph.D. Program in Bioinformatics and Computational Biology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand; Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
  • 3 Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
  • 4 School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor 11800, Pulau Pinang, Malaysia; Natural Product and Drug Discovery Centre, Malaysian Institutes of Pharmaceuticals and Nutraceuticals, National Institutes of Biotechnology Malaysia, Ministry of Science, Technology and Innovation, Block 5-A, Halaman Bukit Gambir, 11700, Penang, Malaysia
  • 5 School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor 11800, Pulau Pinang, Malaysia; Natural Product and Drug Discovery Centre, Malaysian Institutes of Pharmaceuticals and Nutraceuticals, National Institutes of Biotechnology Malaysia, Ministry of Science, Technology and Innovation, Block 5-A, Halaman Bukit Gambir, 11700, Penang, Malaysia. Electronic address: habibahw@usm.my
  • 6 Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
  • 7 Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address: supot.h@chula.ac.th
J Mol Graph Model, 2015 Jul;60:24-33.
PMID: 26086900 DOI: 10.1016/j.jmgm.2015.05.008

Abstract

The pathogenic dengue virus (DV) is a growing global threat, particularly in South East Asia, for which there is no specific treatment available. The virus possesses a two-component (NS2B/NS3) serine protease that cleaves the viral precursor proteins. Here, we performed molecular dynamics simulations of the NS2B/NS3 protease complexes with six peptide substrates (capsid, intNS3, 2A/2B, 4B/5, 3/4A and 2B/3 containing the proteolytic site between P(1) and P(1)' subsites) of DV type 2 to compare the specificity of the protein-substrate binding recognition. Although all substrates were in the active conformation for cleavage reaction by NS2B/NS3 protease, their binding strength was somewhat different. The simulated results of intermolecular hydrogen bonds and decomposition energies suggested that among the ten substrate residues (P(5)-P(5)') the P(1) and P(2) subsites play a major role in the binding with the focused protease. The arginine residue at these two subsites was found to be specific preferential binding at the active site with a stabilization energy of intNS3>2A/2B>4B/5>3/4A>2B/3 in a relative correspondence with previous experimentally derived values.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.