title: SNP analysis of Rac1 For personalized ligand interaction.
abstract: This paper addresses mutational events that give rise to differing response to drugs focusing on Rac1, a protein that has been recognized as a target for drug design for cardiovascular disease due its regulatory role of angiogenesis. Rac1 has been considered with reference to Single Nucleotide Polymorphism (SNP), which has become of great value for personalized medicine. We have considered four variation of Rac1 registered in UNIPROTKB. Two of these variations are due to the environmental or population factors and two are mutation that we have selected because they are located near the binding sites of Rac1. Rac1 has been modelled by Rosetta software and by i-Tasser web server. We have chosen i-Tasser based modelling because the Rac1 structure obtained was more closely resembling crystallography data. In silico model have been used as receptors for docking with a set of 20 morpholines. The results that have been obtained on SNPs shows that a single ligand can react very differently with a mutated structure. Our analysis shows that all mutations that have been considered change Rac1 conformation and increase the accessible surface of Rac1. Our analysis highlights the effect of two sources of genetic variability: single base variation and alternative splicing.
authors.affiliation: Department of Communication, Computer and System Sciences, Nanobiotechnology and Medical Informatics Laboratory University of Genoa, Via all'Opera Pia, 13, 16145, Italy.
authors.forename: Norbert
authors.initials: N
authors.lastname: Maggi
authors.forename: Patrizio
authors.initials: P
authors.lastname: Arrigo
authors.forename: Carmelina
authors.initials: C
authors.lastname: Ruggiero
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D003198:Computer Simulation; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011485:Protein Binding; D011487:Protein Conformation; D017422:Sequence Analysis, DNA / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D020830:rac1 GTP-Binding Protein / Q000737:chemistry* / Q000235:genetics* / Q000648:ultrastructure
chemical_list: D008024:Ligands; D020830:rac1 GTP-Binding Protein