Since EM studies suggested that PNC-27 induces transmembrane pore formation uniquely in cancer cells and our further studies suggested that PNC-27 must bind to HDM-2 in the cancer cells’ membranes to induce tumor cell lysis, we now investigate, using conformational energy analysis, whether PNC-27 can form a low energy complex with the HDM-2 binding domain that is similar in structure for p53 residues 19–29 as determined in the X-ray crystal structure [8] and what the disposition of the leader sequence is in this complex. The gene discussed is TP53; the disease is cancer.