Evolution of High-Affinity Peptide Probes to Detect the SH3 Domain of Cancer Biomarker BCR-ABL

摘要: The BCR–ABL fusion protein is closely associated with the pathological progression of chronic myelogenous leukaemia and some other myeloproliferative diseases, which has long been recognized as one most important cancer biomarkers in tumor diagnosis community. SH3 domain a small, conserved module that specifically recognizes binds proline-rich peptide fragments. In current study, we used synthetic strategy to discover new probes high affinity binding domain. procedure, sequence-based machine learning predictor was developed based on set affinity-known binders, then guide evolutional optimization numerous virtual peptides enrich potency for Subsequently, evolved population generated, from ten highest scores were selected their interaction free energies characterized systematically using combination molecular dynamics simulation energy analysis. Consequently, four suggested promising candidates affinities toward assayed; two peptides, APTYTPPPPP APTYAPPPPP, identified have potent capability dissociation constants K d 3 8 μM, respectively. Further, structural basis energetic property complex examined detail, revealing non-specific SH3–peptide recognition should render broad ligand spectrum