"Chameleonic" backbone hydrogen bonds in protein binding and as drug targets.
We carry out a time-averaged contact matrix study to reveal the existence of protein backbone hydrogen bonds (BHBs) whose net persistence in time differs markedly form their corresponding PDB-reported state. We term such interactions as "chameleonic" BHBs, CBHBs, precisely to account for their tendency to change the structural prescription of the PDB for the opposite bonding propensity in solution. We also find a significant enrichment of protein binding sites in CBHBs, relate them to local water exposure and analyze their behavior as ligand/drug targets. Thus, the dynamic analysis of hydrogen bond propensity might lay the foundations for new tools of interest in protein binding-site prediction and in lead optimization for drug design.
INQUISUR-UNS-CONICET and Departamento de Química, Universidad Nacional del Sur, Avenida Alem 1253, 8000, Bahıa Blanca, Argentina.
C A
CA
Menéndez
INQUISUR-UNS-CONICET and Departamento de Química, Universidad Nacional del Sur, Avenida Alem 1253, 8000, Bahıa Blanca, Argentina.
S R
SR
Accordino
INQUISUR-UNS-CONICET and Departamento de Química, Universidad Nacional del Sur, Avenida Alem 1253, 8000, Bahıa Blanca, Argentina.
D C
DC
Gerbino
INQUISUR-UNS-CONICET and Departamento de Química, Universidad Nacional del Sur, Avenida Alem 1253, 8000, Bahıa Blanca, Argentina. appignan@criba.edu.ar.
G A
GA
Appignanesi
D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000494:pharmacology
D010446:Peptide Fragments; D054852:Small Molecule Libraries; D051736:Proto-Oncogene Proteins c-mdm2
Soft Matter: Interfacial Phenomena and Nanostructured Surfaces