Thesis abstract:

«p»«span style="color:#000000"»«strong»Aims«/strong»«/span»«/p» «p»«span style="color:#000000"»To prioritise novel peptides targeting B-cell receptors (BCR) using de novo in-silico modelling and structural insight from known B-cell receptor ligands«/span»«/p» «p»«span style="color:#000000"»Following synthesis and biological evaluation conducted by collaborators, to evaluate the structure-activity relationship of the identified proteins.«/span»«/p» «p»«span style="color:#000000"» «/span»«/p» «p»«span style="color:#000000"»«strong»Objectives«/strong»«/span»«/p» «p»«span style="color:#000000"»Using artificial intelligence-based methods such as Alpha4Fold2-Multimer, RFDiffuison and RoseTTAFold, to «/span»«span style="color:#231f20"»model BCR for in vitro testing of interactions with potential receptor modulators and inhibitors.«/span»«/p» «p»«span style="color:#231f20"»Design a series of peptides using structure-based drug design (SBDD) by systematically varying factors such as amino acid composition and peptide length to suggest peptides that interact with the receptor.«/span»«/p» «p»«span style="color:#231f20"»Validate generated complexes using atomistic and coarse-grained (CG) molecular dynamics (MD) simulations.«/span»«/p» «p»«span style="color:#231f20"»Compare viable peptides with known BCR ligands.«/span»«/p» «p»«span style="color:#231f20"»Prioritises peptides with identified potential via binding energy calculations for synthesis and further evaluation of the structure-activity relationship.«/span»«/p» «p»«span style="color:#231f20"»Evaluate structure-activity relationships of synthesized peptides in conjunction with known ligands.«/span»«/p» «p» «/p»