In silico analysis unravels the promising anticariogenic efficacy of fatty acids against dental caries causing Streptococcus mutans

Abstract

Globally, dental caries is a prevalent oral disease caused by cariogenic bacteria, primarily Streptococcus mutans. It establishes caries either through sucrose-dependent (via glycosyltransferases) or through sucrose-independent (via surface adhesins Antigen I/II) mechanism. Sortase A (srtA) attaches virulence-associated adhesins to host tissues. Because of their importance in the formation of caries, targeting these proteins is decisive in the development of new anticariogenic drugs. High-throughput virtual screening with LIPID MAPS -a fatty acid database was performed. The selected protein-ligand complexes were subjected to molecular dynamics simulation (MDs). The Binding Free Energy of complexes was predicted using MM/PBSA. Further, the drug-likeness and pharmacokinetic properties of ligands were also analyzed. Out of 46,200 FAs scrutinized virtually against the three protein targets (viz., GtfC, Ag I/II and srtA), top 5 FAs for each protein were identified as the best hit based on interaction energies viz., hydrogen bond numbers and hydrophobic interaction. Further, two common FAs (LMFA01050418 and LMFA01040045) that showed high binding affinity against Ag I/II and srtA were selected for MDs analysis. A 100ns MDs unveiled a stable conformation. Results of Rg signified that FAs does not induce significant structural & conformational changes. SASA indicated that the complexes maintain higher thermodynamic stability during MDs. The predicted binding free energy (MM/PBSA) of complexes elucidated their stable binding interaction. ADME analysis suggested the FAs are biologically feasible as therapeutic candidates. Overall, the presented in silico data is the first of its kind in delineating FAs as promising anticaries agents of future.

Communicated by Ramaswamy H. Sarma

Keywords:

• Dental caries
• S. mutans
• GtfC
• antigen I/II
• Sortase A
• fatty acids
• docking
• ADME profiles
• molecular dynamics

Acknowledgments

The authors thankfully acknowledge the Department of Science and Technology-FIST [Grant No. SR/FST/LSI-639/2015(C)], UGC-SAP [Grant No. F.5-1/2018/DRS-II(SAP-II)], RUSA 2.0 [grant no. F. 24-51/2014-U, Policy (TN Multi-Gen), Dept of Edn, GOI], DST-SERB [File No: EEQ/2020/000288] and ICMR Adhoc Project [File No. 5/4/2-5/Oral Health/2021-NCD-II] for providing instrumentation facilities. RS acknowledges the University Grants Commission, New Delhi India, in the form of UGC-SJSGC (F. No. 82-7/2022(SA-III).

Disclosure statement

The authors declare no conflict of interest.

Author contribution

Ravichellam Sangavi: Designed the research idea, analyzed the data, result interpretation and wrote the original draft. Sankar Muthumanickam: Virtual-screening, in silico result analysis and interpretation. Nambiram Malliagarjuan: helped in analyzing the data and critically revised the original draft. Ravi Jothi: critically revised the original draft. Pandi Boomi: critically revised the original draft. Arivudainambi Seenichamy: critically revised the original draft. Muthusamy Raman: critically revised the original draft. Chaitanya G. Joshi: critically revised the original draft. Shunmugiah Karutha Pandian: critically revised the original draft. Shanmugaraj Gowrishankar: Designed the research idea, analyzed the data, result interpretation and wrote the original draft.

Additional information

Funding

SG gratefully acknowledges Indian Council of Medical Research (ICMR) Adhoc Project Grant (File No. 5/4/2-5/Oral Health/2021-NCD-II) and Department of Science and Technology- Science and Engineering Research Board (DST-SERB)-EEQ Project Grant (File No: EEQ/2020/000288). SG thankfully acknowledges the financial support rendered by RUSA 2.0 [F.24-51/2014-U, Policy (TN Multi-Gen), Department of Education, Government of India].