title: Micro-Environmental Signature of The Interactions between Druggable Target Protein, Dipeptidyl Peptidase-IV, and Anti-Diabetic Drugs.
abstract: OBJECTIVE
  Druggability of a target protein depends on the interacting micro-environment between the target protein and drugs. Therefore, a precise knowledge of the interacting micro-environment between the target protein and drugs is requisite for drug discovery process. To understand such micro-environment, we performed in silico interaction analysis between a human target protein, Dipeptidyl Peptidase-IV (DPP-4), and three anti-diabetic drugs (saxagliptin, linagliptin and vildagliptin).
  
  
  METHODS
  During the theoretical and bioinformatics analysis of micro-environmental properties, we performed drug-likeness study, protein active site predictions, docking analysis and residual interactions with the protein-drug interface. Micro-environmental landscape properties were evaluated through various parameters such as binding energy, intermolecular energy, electrostatic energy, van der Waals'+H-bond+desolvo energy (EVHD) and ligand efficiency (LE) using different in silico methods. For this study, we have used several servers and software, such as Molsoft prediction server, CASTp server, AutoDock software and LIGPLOT server.
  
  
  RESULTS
  Through micro-environmental study, highest log P value was observed for linagliptin (1.07). Lowest binding energy was also observed for linagliptin with DPP-4 in the binding plot. We also identified the number of H-bonds and residues involved in the hydrophobic interactions between the DPP-4 and the anti-diabetic drugs. During interaction, two H-bonds and nine residues, two H-bonds and eleven residues as well as four H-bonds and nine residues were found between the saxagliptin, linagliptin as well as vildagliptin cases and DPP-4, respectively.
  
  
  CONCLUSIONS
  Our in silico data obtained for drug-target interactions and micro-environmental signature demonstrates linagliptin as the most stable interacting drug among the tested anti-diabetic medicines.
authors.affiliation: Institute for Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, Korea; Department of Bio-Informatics, School of Computer and Information Sciences, Galgotias University, Greater Noida, India.
authors.forename: Chiranjib
authors.initials: C
authors.lastname: Chakraborty
authors.affiliation: Departments of Physics, Galgotias College of Engineering and Technology, Greater Noida, India.
authors.forename: Bidyut
authors.initials: B
authors.lastname: Mallick
authors.affiliation: Institute for Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, Korea.
authors.forename: Ashish Ranjan
authors.initials: AR
authors.lastname: Sharma
authors.affiliation: Institute for Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, Korea.
authors.forename: Garima
authors.initials: G
authors.lastname: Sharma
authors.affiliation: Institute for Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, Korea.
authors.forename: Supriya
authors.initials: S
authors.lastname: Jagga
authors.affiliation: Department of Integrative Biology, VIT University, Vellore Tamil Nadu, India.
authors.forename: C George Priya
authors.initials: CG
authors.lastname: Doss
authors.affiliation: Institute for Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, Korea.
authors.forename: Ju-Suk
authors.initials: JS
authors.lastname: Nam
authors.affiliation: Institute for Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, Korea.
authors.forename: Sang-Soo
authors.initials: SS
authors.lastname: Lee
keywords: Dipeptidyl Peptidase-IV (DPP-4); Linagliptin; Saxagliptin; Vildagliptin