PMID- 38321931
OWN - NLM
STAT- Publisher
LR  - 20240207
IS  - 1538-0254 (Electronic)
IS  - 0739-1102 (Linking)
DP  - 2024 Feb 7
TI  - Computational study of the piperidine and FtsZ interaction in Salmonella Typhi: 
      implications for disrupting cell division machinery.
PG  - 1-14
LID - 10.1080/07391102.2024.2314272 [doi]
AB  - FtsZ, a bacterial cell division protein, is essential for assembling the 
      contractile Z-ring crucial in bacterial cytokinesis. Consequently, inhibiting 
      FtsZ could impede proto-filaments, disrupting FtsZ and other associated proteins 
      vital for cell division machinery. Conduct an in-silico drug interaction study to 
      identify novel drug candidates that inhibit the FtsZ protein, aiming to prevent 
      Multi-Drug Resistant (MDR) Salmonella Typhi. Data mining was performed based on 
      piperidine compounds, which were subsequently screened for safe pharmacokinetic 
      profiles. Compounds that met favorable drug-likeness criteria underwent virtual 
      screening against the FtsZ drug target. Two compounds were chosen for molecular 
      docking and molecular dynamic simulation to verify the binding affinity and 
      stability between the target protein and the potential compounds. The 400 
      isoforms of piperidine analogues were curated, among them potent compound 
      ZINC000000005416 found to possess high binding affinity (-8.49 kcal/mol) and low 
      dissociation constant (0.597 microM). The highest binding affinity shown by 
      ZINC000000005416 was validated by hydrogen bonds, hydrophobic interaction, and 
      salt bridges with the functional domain of the cell division regulatory protein. 
      Docking profiles, when correlated with molecular dynamic simulation (MDS) 
      depicted stable trajectories and compatible conformational changes in the 
      FtsZ-ZINC000000005416 complex. The stable simulated trajectories were validated 
      through free-energy calculations using the Molecular Mechanics-Poisson Boltzmann 
      Surface Area (MM/PBSA) module. Low energy conformations, although the simulation 
      trajectory confirmed the stable ZINC000000005416-FtsZ interaction, which 
      encouraged experimental validations. This study encourages further exploration of 
      the compound ZINC000000005416 as a drug candidate inhibiting FtsZ protein against 
      MDR Salmonella Typhi.Communicated by Ramaswamy H. Sarma.
FAU - Kumar, Hithesh
AU  - Kumar H
AUID- ORCID: 0000-0002-2452-5237
AD  - Department of Bio-Sciences, School of Biosciences and Technology (SBST), Vellore 
      Institute of Technology, Vellore, India.
AD  - Medical and Biological Computing Laboratory, Department of Biotechnology, School 
      of Biosciences and Technology (SBST), Vellore Institute of Technology, Vellore, 
      India.
FAU - Manoharan, Anand
AU  - Manoharan A
AUID- ORCID: 0000-0001-9130-8016
AD  - Department of Paediatrics, The CHILDS Trust Medical Research Foundation, Kanchi 
      Kamakoti CHILDS Trust Hospital, Chennai, India.
FAU - Anbarasu, Anand
AU  - Anbarasu A
AUID- ORCID: 0000-0003-2216-7488
AD  - Medical and Biological Computing Laboratory, Department of Biotechnology, School 
      of Biosciences and Technology (SBST), Vellore Institute of Technology, Vellore, 
      India.
FAU - Ramaiah, Sudha
AU  - Ramaiah S
AUID- ORCID: 0000-0002-4800-329X
AD  - Department of Bio-Sciences, School of Biosciences and Technology (SBST), Vellore 
      Institute of Technology, Vellore, India.
AD  - Medical and Biological Computing Laboratory, Department of Biotechnology, School 
      of Biosciences and Technology (SBST), Vellore Institute of Technology, Vellore, 
      India.
LA  - eng
PT  - Journal Article
DEP - 20240207
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
SB  - IM
OTO - NOTNLM
OT  - Enteric fever
OT  - molecular docking
OT  - multidrug resistance
OT  - simulations
OT  - structural dynamics
OT  - virtual screening
EDAT- 2024/02/07 06:42
MHDA- 2024/02/07 06:42
CRDT- 2024/02/07 03:34
PHST- 2024/02/07 06:42 [medline]
PHST- 2024/02/07 06:42 [pubmed]
PHST- 2024/02/07 03:34 [entrez]
AID - 10.1080/07391102.2024.2314272 [doi]
PST - aheadofprint
SO  - J Biomol Struct Dyn. 2024 Feb 7:1-14. doi: 10.1080/07391102.2024.2314272.