Binding hot-spots in an antibody–ssDNA interface: a molecular dynamics study

Abstract

Simulating antigen-antibody interactions is essential for elucidating antigen-antibody mechanics. Proteins interactions are vital for elucidating antibody-ssDNA associations in immunology. Therefore, this study investigated the dissociation of the human systemic lupus erythematosus antibody-ssDNA complex structure. Dissociation (i.e. the distance between the center of mass of the ssDNA and the antibody) is also studied using the potential of mean force calculations based on molecular dynamics and the explicit water model. The MM-PBSA method is also used to prove our dissociation simulations. With 605 nanosecond molecular dynamics simulations, the results indicate that the 8 residues (i.e. Gly44 (HCDR2), Asn54 (HCDR2), Arg98 (HCDR3), Tyr100 (HCDR3), Asp101 (HCDR3), Tyr32 (LCDR1), Tyr49 (LCDR2) and Asn50 (LCDR2)), and the five inter-protein molecular hydrogen bonds may profoundly impact the antibody-ssDNA interaction, a finding which may be useful for protein engineering of this antibody-ssDNA structure. Experimental binding affinity of this antibody-ssDNA complex equals 7.00 kcal mol(-1). Our dissociation binding affinity is 7.96 ± 0.33 kcal mol(-1) and MM-PBSA binding affinity is 9.12 ± 1.65 kcal mol(-1), which is close to the experimental value. Additionally, the 8 residues Gly44 (HCDR2), Asn54 (HCDR2), Arg98 (HCDR3), Tyr100 (HCDR3), Asp101 (HCDR3), Tyr32 (LCDR1), Tyr49 (LCDR2) and Asn50 (LCDR2) may play a more significant role in developing bioactive antibody analogues.

Synthetic Oligonucleotide Probes for Detection of Autoimmune Antibodies

“…Rapid development of synthetic biology and imaging techniques allows rational design and preparation of advanced nucleic acid sensors addressing diverse research and clinical tasks on autoimmune diseases. Advanced computational chemistry integrated with existing empirical data plays an important role for this field, since molecular simulations, supported by recent studies on antibody-DNA binding process, provide structural considerations for the new synthetic sensors with high target selectivity, brightness and binding affinity [56]. Another vital aspect for development of new biosensors is a close interdisciplinary collaboration between synthetic chemists and clinical community [57].…”

Disruption of protein–protein interactions: hot spot detection, structure-based virtual screening and in vitro testing for the anti-cancer drug target – survivin

“…22 These in silico tools are fast, reliable, and successfully used by various scientic groups. [25][26][27][28][29] Survivin is an IAP family protein and plays a multifunctional role in cell division and apoptosis by interacting with its substrate proteins, including Aurora B, INCENP, borealin, CDK4, heat shock proteins (HSP), X-linked inhibitor of apoptosis protein (XIAP), caspase enzymes, and other proteins. [30][31][32][33][34][35] Over expression of survivin has been observed in many of human solid tumors, but not in normal adult cells.…”