Graph-based algorithms for dynamic hydrogen-bond networks

Dynamic hydrogen(H)-bonds and hydrogen-bond networks provide proteins with structural plasticity required for function. Proteins for which dynamic H-bond networks are particularly important for function include protonation-coupled membrane receptors and transporters. In such proteins, it is commonly thought that extended networks of protein and protein-water H-bonds assemble transiently to establish allosteric communication between distinct regions of the protein, to bind and conduct protons. The dynamic nature of such networks, and the relatively large size of many membrane receptors and transporters of direct interest to human health and disease, raise the challenges of how to compute and analyze efficiently the H-bond interaction networks, how to rank the relative importance of protein groups for allosteric protein couplings, and how to begin to predict titratable protein sidechains where protonation change might occur during protein function.

We develop graph-based algorithms to compute H-bond networks from datasets of protein structures from structural biology and from numerical simulations. We apply these algorithms to decipher the role of dynamical H-bond networks in the reaction mechanisms of protonation-coupled proteins and peptides.

People involved

Prof. Ana-Nicoleta Bondar

Associated member

  • Institute for Advanced Simulation (IAS)
  • Institute of Neurosciences and Medicine (INM)
  • Computational Biomedicine (IAS-5 / INM-9)
E-Mail
  • Institute for Advanced Simulation (IAS)
  • Computational Biomedicine (IAS-5 / INM-9)
Building 16.15 /
Room R 3010
+49 2461/61-8941
E-Mail

Hoa Thi Nguyen

Ph.D. student

  • Institute for Advanced Simulation (IAS)
  • Computational Biomedicine (IAS-5 / INM-9)
Building 16.15 /
Room 3006a
+49 2461/61-8924
E-Mail

Dr. Emiliano Ippoliti

Staff member and IT coordinator

  • Institute for Advanced Simulation (IAS)
  • Computational Biomedicine (IAS-5 / INM-9)
Building 16.15 /
Room 2005
+49 2461/61-8920
E-Mail

Collaborators

  • Prof. Dr. William C.  Wimley (Tulane University)
  • Prof. Dr. Kalina Hristova (Johns Hopkins University)

References

  1. Graph-based algorithms to dissect protein conformational dynamics. Bondar A-N (2022). J Phys Chem B 126, 3973-3984.
  2. Algorithm to catalogue topologies of dynamic lipid hydrogen-bond networks. Karathanou K, Bondar A-N (2022). BBA-Biomembranes 1864, 183859.
  3. Conserved hydrogen-bond motifs of membrane transporters and receptors. Lazaratos M, Siemers M, Brown LS, Bondar A-N (2022). BBA-Biomembranes 1864, 183896.
  4. C-Graphs tool with graphical user interface to dissect conserved hydrogen-bond networks: applications to visual rhodopsins. Bertalan É, Lesca E, Schertler GFX, Bondar A-N (2021). J Chem Inf Model 61, 3692-5707.
  5. Interactive interface for graph-based analyses of dynamic hydrogen-bond networks: application to spike protein. S. Siemers M, Bondar A-N (2021) J Chem Inf Model 61, 2998-3014.
  6. Bridge: a graph-based algorithm to analyze dynamic H-bond networks in membrane proteins. Siemers M, Lazaratos M, Karathanou K, Guerra F, Brown LS, Bondar A-N (2019). J Chem Theory Comput 15, 6781-6798.
Last Modified: 03.03.2023