title: Homology-based Modeling of Rhodopsin-like Family Members in the Inactive State: Structural Analysis and Deduction of Tips for Modeling and Optimization.
abstract: Modeling G-Protein Coupled Receptors (GPCRs) is an emergent field of research, since utility of high-quality models in receptor structure-based strategies might facilitate the discovery of interesting drug candidates. The findings from a quantitative analysis of eighteen resolved structures of rhodopsin family "A" receptors crystallized with antagonists and 153 pairs of structures are described. A strategy termed endeca-amino acids fragmentation was used to analyze the structures models aiming to detect the relationship between sequence identity and Root Mean Square Deviation (RMSD) at each trans-membrane-domain. Moreover, we have applied the leave-one-out strategy to study the shiftiness likelihood of the helices. The type of correlation between sequence identity and RMSD was studied using the aforementioned set receptors as representatives of membrane proteins and 98 serine proteases with 4753 pairs of structures as representatives of globular proteins. Data analysis using fragmentation strategy revealed that there is some extent of correlation between sequence identity and global RMSD of 11AA width windows. However, spatial conservation is not always close to the endoplasmic side as was reported before. A comparative study with globular proteins shows that GPCRs have higher standard deviation and higher slope in the graph with correlation between sequence identity and RMSD. The extracted information disclosed in this paper could be incorporated in the modeling protocols while using technique for model optimization and refinement.
authors.affiliation: Department of Drug Sciences.|Department of Chemical Sciences -, University of Catania -, V.le A.Doria 6, I-95125, Catania, Italy.
authors.forename: Matteo
authors.identifier: 0000-0001-6623-2849
authors.initials: M
authors.lastname: Pappalardo
authors.affiliation: Institute of Applied Research - Galilee Society, Galeel street, Shefa-Amr, 20200, Israel.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Rayan
authors.affiliation: Faculty of Pharmacy, Al-Quds University, Abu-Dies, Palestine.
authors.forename: Saleh
authors.initials: S
authors.lastname: Abu-Lafi
authors.affiliation: Department of Drug Sciences.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Leonardi
authors.affiliation: National Research Council, Institute of Biostructures and Bioimages, Via. P. Gaifami 18, 95126, Catania, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Milardi
authors.affiliation: Department of Drug Sciences.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Guccione
authors.affiliation: Institute of Applied Research - Galilee Society, Galeel street, Shefa-Amr, 20200, Israel.|Drug Discovery Informatics Lab, Qasemi-Research Center, Al-Qasemi Academic College, Baka El-Garbiah, 30100, Israel.
authors.forename: Anwar
authors.initials: A
authors.lastname: Rayan
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry; D012243:Rhodopsin / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D043562:Receptors, G-Protein-Coupled; D012243:Rhodopsin
keywords: Bioinformatics; GPCRs; Homology Modeling; Structure-based modeling