• Jump to content
  • Jump to navigation
  • Jump to bottom of page
Simulate organization breadcrumb open Simulate organization breadcrumb close
  • FAUTo the central FAU website
  • RRZE
  • NHR-Geschäftsstelle
  • Gauß-Allianz

Navigation Navigation close
  • News
  • People
  • Research
    • Research Focus
    • Publications, Posters and Talks
    • Software & Tools
    • HPC Performance Lab
    • Atomic Structure Simulation Lab
    • NHR PerfLab Seminar
    • Projects
    • Awards
    Portal Research
  • Teaching & Training
    • Lectures and Seminars
    • Tutorials and Courses
    • Theses
    • HPC Cafe
    • Student Cluster Competition
    Portal Teaching
  • Systems & Services
    • Systems, Documentation & Instructions
    • Support & Contact
    • Success Stories from the Support
    • Training Resources
    • Summary of System Utilization
    • Reports from User Projects
    Portal Systems & Services

  1. Home
  2. Systems & Services
  3. User projects
  4. Biology, life sciences & pharmaceutics
  5. HPC User Report from C. Söldner (Professorship for Bioinformatics)

HPC User Report from C. Söldner (Professorship for Bioinformatics)

In page navigation: Systems & Services
  • Systems, Documentation & Instructions
    • Getting started with HPC
      • NHR@FAU HPC-Portal Usage
    • NHR application rules – NHR@FAU
    • HPC clusters & systems
      • Dialog server
      • Alex GPGPU cluster (NHR+Tier3)
      • Fritz parallel cluster (NHR+Tier3)
      • Meggie parallel cluster (Tier3)
      • Emmy parallel cluster (Tier3)
      • Woody throughput cluster (Tier3)
      • TinyFat cluster (Tier3)
      • TinyGPU cluster (Tier3)
      • Test cluster
      • Jupyterhub
    • SSH – Secure Shell access to HPC systems
    • File systems
    • Batch Processing
      • Job script examples – Slurm
      • Advanced topics Slurm
      • Torque batch system
    • Software environment
    • Special applications, and tips & tricks
      • Amber/AmberTools
      • ANSYS CFX
      • ANSYS Fluent
      • ANSYS Mechanical
      • Continuous Integration / Gitlab Cx
      • CP2K
      • CPMD
      • GROMACS
      • IMD
      • Intel MKL
      • LAMMPS
      • Matlab
      • NAMD
      • OpenFOAM
      • ORCA
      • Python and Jupyter
      • Quantum Espresso
      • R and R Studio
      • STAR-CCM+
      • Tensorflow and PyTorch
      • TURBOMOLE
      • VASP
        • Request access to central VASP installation
      • Working with NVIDIA GPUs
      • WRF
  • Support & Contact
    • Monthly HPC Cafe
    • HPC Performance Lab
    • Atomic Structure Simulation Lab
    • Support Success Stories
      • Success story: Elmer/Ice
  • HPC User Training
  • HPC System Utilization
  • User projects
    • Biology, life sciences & pharmaceutics
      • HPC User Report from A. Bochicchio (Professorship of Computational Biology)
      • HPC User Report from A. Horn (Bioinformatics)
      • HPC User Report from C. Söldner (Professorship for Bioinformatics)
      • HPC User Report from J. Calderón (Computer Chemistry Center)
      • HPC User Report from J. Kaindl (Chair of Medicinal Chemistry)
      • HPC User Report from K. Pluhackova (Computational Biology Group)
    • Chemical & mechanical engineering
      • HPC User Report from A. Leonardi (Institute for Multiscale Simulation)
      • HPC User Report from F. Lenahan (Institute of Advanced Optical Technologies – Thermophysical Properties)
      • HPC User Report from F. Weber (Chair of Applied Mechanics)
      • HPC User Report from K. Nusser (Institute of Process Machinery and Systems Engineering)
      • HPC User Report from K. Nusser (Institute of Process Machinery and Systems Engineering)
      • HPC User Report from L. Eckendörfer (Catalytic Reactors and Process Technology)
      • HPC User Report from M. Klement (Institute for Multiscale Simulation)
      • HPC User Report from M. Münsch (Chair of Fluid Mechanics)
      • HPC User Report from T. Klein (Institute of Advanced Optical Technologies – Thermophysical Properties)
      • HPC User Report from T. Schikarski (Chair of Fluid Mechanics / Chair of Particle Technology)
      • HPC User Report from U. Higgoda (Institute of Advanced Optical Technologies – Thermophysical Properties)
    • Chemistry
      • HPC User Report from B. Becit (Professorship of Theoretical Chemistry)
      • HPC User Report from B. Meyer (Computational Chemistry – ICMM)
      • HPC User Report from D. Munz (Chair of Inorganic and General Chemistry)
      • HPC User Report from J. Konrad (Professorship of Theoretical Chemistry)
      • HPC User Report from P. Schwarz (Interdisciplinary Center for Molecular Materials)
      • HPC User Report from S. Frühwald (Chair of Theoretical Chemistry)
      • HPC User Report from S. Maisel (Chair of Theoretical Chemistry)
      • HPC User Report from S. Sansotta (Professorship of Theoretical Chemistry)
      • HPC User Report from S. Seiler (Interdisciplinary Center for Molecular Materials)
      • HPC User Report from S. Trzeciak (Professorship of Theoretical Chemistry)
      • HPC User Report from T. Klöffel (Interdisciplinary Center for Molecular Materials)
      • HPC User Report from T. Kollmann (Professorship of Theoretical Chemistry)
    • Computer science & Mathematics
      • HPC User Report from B. Jakubaß & S. Falk (Division of Phoniatrics and Pediatric Audiology)
      • HPC User Report from D. Schuster (Chair for System Simulation)
      • HPC User Report from F. Wein (Professorship for Mathematical Optimization)
      • HPC User Report from J. Hornich (Professur für Höchstleistungsrechnen)
      • HPC User Report from L. Folle and K. Tkotz (Chair of Computer Science 5, Pattern Recognition)
      • HPC User Report from R. Burlacu (Economics, Discrete Optimization, and Mathematics)
      • HPC User Report from S. Falk (Division of Phoniatrics and Pediatric Audiology)
      • HPC User Report from S. Falk (Phoniatrics and Pediatric Audiology)
      • HPC User Report from S. Jacob (Chair of System Simulation)
    • Electrical engineering & Audio processing
      • HPC User Report from N. Pia (AudioLabs)
      • HPC User Report from S. Balke (Audiolabs)
    • Geography & Climatology
      • HPC usage report from F. Temme, J. V. Turton, T. Mölg and T. Sauter
      • HPC usage report from J. Turton, T. Mölg and E. Collier
      • HPC usage report from N. Landshuter, T. Mölg, J. Grießinger, A. Bräuning and T. Peters
      • HPC User Report from C. Pickler and T. Mölg (Climate System Research Group)
      • HPC User Report from E. Collier (Climate System Research Group)
      • HPC User Report from E. Collier and T. Mölg (Climate System Research Group)
      • HPC User Report from E. Collier, T. Sauter, T. Mölg & D. Hardy (Climate System Research Group, Institute of Geography)
      • HPC User Report from E. Kropač, T. Mölg, N. J. Cullen, E. Collier, C. Pickler, and J. V. Turton (Climate System Research Group)
      • HPC User Report from J. Fürst (Department of Geography)
      • HPC User Report from P. Friedl (Department of Geography)
      • HPC User Report from T. Mölg (Climate System Research Group)
    • Linguistics
      • HPC User Report from P. Uhrig (Chair of English Linguistics)
    • Material sciences
      • HPC User Report from A. Rausch (Chair of Materials Science and Engineering for Metals)
      • HPC User Report from D. Wei (Chair of Materials Simulation)
      • HPC User Report from J. Köpf (Chair of Materials Science and Engineering for Metals)
      • HPC User Report from P. Baranova (Chair of General Materials Properties)
      • HPC User Report from S. Nasiri (Chair for Materials Simulation)
      • HPC User Report from S.A. Hosseini (Chair for Materials Simulation)
    • Medical research
      • HPC User Report from H. Sadeghi (Phoniatrics and Pediatric Audiology)
      • HPC User Report from P. Ritt (Imaging and Physics Group, Clinic of Nuclear Medicine)
      • HPC User Report from S. Falk (Division of Phoniatrics and Pediatric Audiology)
    • Physics
      • HPC User Report from D. Jankowsky (High-Energy Astrophysics)
      • HPC User Report from M. Maiti (Inst. Theoretische Physik 1)
      • HPC User Report from N. Vučemilović-Alagić (PULS group of the Physics Department)
      • HPC User Report from O. Malcioglu (Theoretische Festkörperphysik)
      • HPC User Report from S. Fey (Chair of Theoretical Physics I)
      • HPC User Report from S. Ninova (Theoretical Solid-State Physics)
      • HPC User Report from S. Schmidt (Erlangen Centre for Astroparticle Physics)
    • Regional users and student projects
      • HPC User Report from Dr. N. Ferruz (University of Bayreuth)
      • HPC User Report from J. Martens (Comprehensive Heart Failure Center / Universitätsklinikum Würzburg)
      • HPC User Report from M. Fritsche (HS-Coburg)
      • HPC User Report from M. Heß (TH-Nürnberg)
      • HPC User Report from M. Kögel (TH-Nürnberg)
  • NHR compute time projects

HPC User Report from C. Söldner (Professorship for Bioinformatics)

Histamine binding and activation of the H1 receptor

Contact:

Christian A. Söldner (M.Sc.)
Division of Bioinformatics
Friedrich-Alexander-Universität Erlangen-Nürnberg

Mainly used HPC resources at RRZE

Large scale conventional MD simulations on Meggie, GaMD simulations on TinyGPU.

The histamine H1 receptor (H1R) plays an important role in the context of hypersensitivity reactions and is therefore a main target of antiallergic drugs. Using molecular dynamics (MD) simulations, we intend to unveil details of histamine binding to the H1R and the associated activation of the receptor.

Motivation and problem definition

An excessive stimulation of the H1R by its physiological ligand histamine is coupled to some key symptoms of allergies such as sneezing, pruritus, overproduction of mucus, or even severe reactions like anaphylactic shock. For the design of interfering medications, it is an important prerequisite to gather precise knowledge about the molecular processes involved. Especially the histamine binding pose and the specific underlying interactions with the receptor are of particular interest for pharmaceutical research. Since there exists no crystal structure of the H1R in complex with histamine, we used conventional MD simulations to simulate spontaneous binding of histamine to the receptor and to characterize the binding site in more detail. Moreover, we are currently performing Gaussian accelerated MD (GaMD) simulations to study the conformational changes which might arise upon binding, i.e. the receptor activation which is necessary for downstream intracellular signaling.

Methods and codes

Binding pose of histamine within the orthosteric binding site of the H1R according to our spontaneous binding simulation. The protein backbone is shown in light blue, histamine is shown as sticks with the carbon atoms colored in green. The side chains of the most important interacting residues of the H1R are also displayed as sticks, with their carbon atoms colored in orange.

For conventional MD simulations, we mainly use the GROMACS program suite, which offers exceptionally good scaling on MPI-parallel CPU nodes. With 25 nodes on Meggie, an average simulation speed of more than 200 ns/day can be obtained for GPCR systems. Moreover, we are currently running GaMD simulations implemented in AMBER. GaMD is an enhanced sampling algorithm which allows to overcome barriers in the free energy landscape by addition of a Gauss-shaped bias potential to the energy function of the system. Thereby, structural changes that would otherwise be very rare may be observed in significantly reduced simulation time. AMBER can be efficiently run on single GPUs combining thus high simulation speed with less energy consumption and a decreased use of computational resources.

Results

Using conventional MD simulations, we were able to observe a spontaneous binding event of histamine to the H1R. After initial contacts with the extracellular loop 2, the ligand moved first into the vestibule of the binding pocket and then further downwards to the orthosteric binding site. Additional equilibrium MD simulations on a microsecond time scale were used to prove that the determined binding mode is stable and to quantify the most important interacting residues. The obtained data are in good agreement with previous docking studies and site-directed mutagenesis experiments. The final binding mode was shown to be especially characterized by a salt bridge between the ammonium nitrogen atom of histamine and the conserved Asp1073.32. To analyze the relevance of this particular residue for ligand binding, we also performed MD simulations of a histamine-bound D107A mutant receptor, in which we observed that the ligand was much more flexible and that it even dissociated in one of the runs.

Outreach

Christian A. Söldner, Anselm H. C. Horn, Heinrich Sticht, “Binding of histamine to the H1 receptor—a molecular dynamics study”, J Mol Model 2018, 24: 346, DOI: 10.1007/s00894-018-3873-7

Researcher’s Bio and Affiliation

Christian A. Söldner obtained his degree in Molecular Medicine at FAU. After his master’s thesis in the bioinformatics group at the medical faculty’s institute of biochemistry (Prof. Heinrich Sticht), he is currently striving to finalize his Ph.D. thesis in the same group. As a graduate of the GRK1910, his research is mainly focused on the analysis of receptor-ligand interactions.

Erlangen National High Performance Computing Center (NHR@FAU)
Martensstraße 1
91058 Erlangen
Germany
  • Imprint
  • Privacy
  • Accessibility
  • How to find us
Up