title: Structure-Based Drug Designing and Simulation Studies for Finding Novel Inhibitors of Heat Shock Protein (HSP70) as Suppressors for Psoriasis.
abstract: Psoriasis is a chronic immune-mediated inflammatory skin disorder. Heat shock proteins (HSPs) have been witnessed as a potential drug target for inhibition of psoriatic cell differentiation. The expression level of HSP is increased when the cells get exposed to elevated temperature, oxidative stress and nutritional deficiencies and thus plays major role in psoriatic progression pathway. Immunoreactivity intensity distribution index scores for HSP70 expression is significantly higher in psoriatic patients compared to normal. In the present work, the 3D structure of human Hsp70 has been taken. Inhibition of HSP70 can control the severity of psoriasis up to many folds; thus, virtual screening was performed against lead-like, drug-like and some natural product of ZINC database. The screened ligands were further introduced to ADMET prediction and simulations to see the drug proficiency and likeness property. The molecular dynamic of system was found stable during simulation trajectory and not much of significant changes occurred in the conformation of the protein-ligand complex. Thus, present study in all probability might prove useful for future design of new derivatives with higher potency and specificity.
authors.affiliation: Indian Institute of Information Technology, Allahabad, India.
authors.forename: Sonali
authors.initials: S
authors.lastname: Mishra
authors.affiliation: Gautam Buddha University, New Delhi, India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Indian Institute of Information Technology, Allahabad, India.
authors.forename: Pritish Kumar
authors.initials: PK
authors.lastname: Varadwaj
authors.affiliation: Indian Institute of Information Technology, Allahabad, India. kmisra@iiita.ac.in.
authors.forename: Krishna
authors.initials: K
authors.lastname: Misra
mesh_terms: D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D055550:Protein Stability; D011565:Psoriasis / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008024:Ligands
keywords: Autoimmune; HSP70 (Heat shock protein 70); IRIDI (Immunoreactivity intensity distribution index); Inhibitors; Psoriasis