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

• Computational Biomedicine (INM-9)

E-Mail

Prof. Dr. Paolo Carloni

Director

• Institute of Neurosciences and Medicine (INM)
• Computational Biomedicine (INM-9)

Building 16.15 /
Room R 3010

+49 2461/61-8941

E-Mail

Hoa Thi Nguyen

Ph.D. student

• Institute of Neurosciences and Medicine (INM)
• Computational Biomedicine (INM-9)

Building 16.15 /
Room 3006a

02461618924

E-Mail

Dr. Emiliano Ippoliti

Staff member and IT coordinator

• Institute of Neurosciences and Medicine (INM)
• Computational Biomedicine (INM-9)

Building 16.15 /
Room 2005

+49 2461/61-8920

E-Mail

Éva Bertalan

Ph.D. student

E-Mail

Ioana Dumitru

Ph.D. student

E-Mail

Alina Halaicu

Ph.D. student

E-Mail

Denisa Sonia Andronic

Master student

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.