[et_pb_section fb_built=”1″ _builder_version=”4.20.4″ _module_preset=”default” use_background_color_gradient=”on” background_color_gradient_direction=”140deg” background_color_gradient_stops=”#004872 0%|rgba(41,17,96,0.8) 100%” background_color_gradient_overlays_image=”on” background_color_gradient_start=”#004872″ background_color_gradient_end=”rgba(41,17,96,0.8)” min_height=”325px” hover_enabled=”0″ global_colors_info=”{}” theme_builder_area=”post_content” background_enable_image=”off” sticky_enabled=”0″][et_pb_row _builder_version=”4.16″ _module_preset=”default” custom_padding=”60px|||||” global_colors_info=”{}” theme_builder_area=”post_content”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}” theme_builder_area=”post_content”][et_pb_text _builder_version=”4.16″ _module_preset=”default” header_font=”Roboto|500|||||||” header_text_color=”#FFFFFF” header_font_size=”44px” min_height=”28px” global_colors_info=”{}” theme_builder_area=”post_content”]<\/p>\n
[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}” theme_builder_area=”post_content”][et_pb_row _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}” theme_builder_area=”post_content”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}” theme_builder_area=”post_content”][et_pb_text _builder_version=”4.20.4″ _module_preset=”default” hover_enabled=”0″ custom_css_before=”||||” global_colors_info=”{}” theme_builder_area=”post_content” sticky_enabled=”0″]<\/p>\n
O.1 Characterization of h\u03b3D-p23T:\u03b1B-Crys interaction<\/strong><\/p>\n In order to better understand how structural changes in the P23T variant of h\u03b3D-Crys lead to congenital cataract, we carry out comparative protein-protein interaction studies between wild-type h\u03b3D-Crys, and h\u03b3D-P23T, with small heat shock chaperone \u03b1B-Crys. The interaction differences will provide a molecular framework for understanding whether the protein aggregation associated with the cataract is a direct property of the mutation, or may reflect an inability to be recognized by the \u03b1-Crys chaperone. In order to gain new insights whether \u03b1B-Crys is able to suppress to the aggregation of h\u03b3D-p23T mutant, we use solution NMR. Suppression levels of h\u03b3D-p23T aggregation in the presence of \u03b1B-Crys will be monitored as a function of increasing chaperone: mutant molar ratio.<\/p>\n \u00a0O.2 In silico inhibitors screening of h\u03b3D-P23T aggregation<\/strong><\/p>\n We aim to identify novel suppression inhibitors against h\u03b3D-P23T aggregation, using in silico<\/em> compounds screening. The potential inhibitors of h\u03b3D-P23T aggregation will be searched through docking subset of compound found in ZINC15, a public access database of commercially available compounds. Subsequently, the best performing ones will be further analyzed by molecular dynamics simulations to improve docking results. A m<\/span>olecular docking based on shape complementarity will be carried out to subset rank in term of free energy score, and predicted affinity to the binding cleft of the protein.<\/p>\n \u00a0O.3 Suppression bioassay of h\u03b3D-P23T aggregation<\/strong><\/p>\n Inhibitors aggregation suppression in vitro<\/em> will be performed using turbidity bioassay, protein-ligand binding NMR studies in solution, ITC, and molecular docking. Combining in silico<\/em> tools, with aggregation suppression bioassays, will reduce time and cost afferent to high-throughput library screening.<\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":" ObjectivesO.1 Characterization of h\u03b3D-p23T:\u03b1B-Crys interaction In order to better understand how structural changes in the P23T variant of h\u03b3D-Crys lead to congenital cataract, we carry out comparative protein-protein interaction studies between wild-type h\u03b3D-Crys, and h\u03b3D-P23T, with small heat shock chaperone \u03b1B-Crys. The interaction differences will provide a molecular framework for understanding whether the protein aggregation […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"class_list":["post-37","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/www.itim-cj.ro\/PNCDI\/antictract\/wp-json\/wp\/v2\/pages\/37","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.itim-cj.ro\/PNCDI\/antictract\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.itim-cj.ro\/PNCDI\/antictract\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.itim-cj.ro\/PNCDI\/antictract\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.itim-cj.ro\/PNCDI\/antictract\/wp-json\/wp\/v2\/comments?post=37"}],"version-history":[{"count":2,"href":"https:\/\/www.itim-cj.ro\/PNCDI\/antictract\/wp-json\/wp\/v2\/pages\/37\/revisions"}],"predecessor-version":[{"id":40,"href":"https:\/\/www.itim-cj.ro\/PNCDI\/antictract\/wp-json\/wp\/v2\/pages\/37\/revisions\/40"}],"wp:attachment":[{"href":"https:\/\/www.itim-cj.ro\/PNCDI\/antictract\/wp-json\/wp\/v2\/media?parent=37"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}