Investigating small molecule compounds targeting psoriasis based on cMAP database and molecular dynamics simulation

Abstract

Objective Psoriasis (PSO) is a chronic inflammatory skin disease that severely affects the physical and mental health of patients. Drug resistance has been developed upon current drug treatments, and there is no specific therapy. The aim of this study was to screen promising novel drug candidates for PSO using molecular dynamics (MD) simulations. Methods The data of PSO were downloaded from gene expression omnibus (GEO) database and subjected to variance analysis. Target proteins and small molecule compounds targeting PSO were predicted in the connective map (cMAP) database. Molecular docking, MD simulation, and trajectory analysis were conducted to predict the binding of target proteins to compounds. Results 1999 differentially expressed genes in PSO were obtained by differential analysis. Through cMAP database prediction, a low Score value of −45.69 for lymphocyte cell‐specific protein‐tyrosine kinase (LCK) was revealed, and aminogenistein was identified as the compound targeting LCK, and LCK was notably highly expressed in the PSO samples. The drugScore of the binding pocket P_0 was 0.814656, which was docked with aminogenistein. The results showed that there were more than one binding site between LCK and aminogenistein with binding energy less than −7.0 kJ/mol, and the docking was relatively stable. The results of root‐mean‐square deviation (RMSD), root‐mean‐square fluctuation (RMSF), Gyrate, number of hydrogen bonds and total free binding energy in MD simulations showed that the binding of aminogenistein to LCK was relatively solid. Conclusion Aminogenistein has good protein‐ligand interaction and stability with LCK, a target of PSO, and is a novel drug candidate for PSO.

Analysis of the anti-Alzheimer potential of bioactive compounds from Citrus hystrix DC. peel, leaf, and essential oil by network pharmacology

“…The evaluation included assessing the RMSD of protein backbone Cα atoms, ligand conformation, and movement from the binding pocket. RMSD is used in molecular dynamics studies to measure the distance between atoms over time and evaluate the structural stability of protein-ligand complexes [ [106] , [107] , [108] , [109] ]. Good structural stability is indicated by low deviation or an RMSD of 1–4 Å [ 55 ].…”

Integrated analysis of the role of PR/SET domain 14 in gastric cancer

“…The half-maximal inhibitory concentrations (IC50) representing the drug response were estimated using the pRRophetic package [ 21 ]. Upregulated and downregulated DEGs were uploaded to the cMAP database ( https://clue.io ) to identify potential drugs for the treatment of GC [ 22 ] and matched with small-molecule therapies. Four important small-molecule drugs and their enrichment scores were listed.…”

Identification of common mechanisms and biomarkers for dermatomyositis and atherosclerosis based on bioinformatics analysis

“…The limma package, 22 within the R software environment (Version 4.3.2), was deployed to identify differentially expressed genes (DEGs) between patients with DM and healthy controls, as well as between patients with arteriosclerosis and healthy controls, as referenced in studies. 23 , 24 , 25 , 26 DEGs were filtered based on the criteria of an absolute |log FC| > 1 and adjusted p‐ value < 0.05…”