Welcome to the official TIGER2h(s)_PE repository

Please find here the latest TIGER2h_PE and TIGER2hs_PE implementations for hybrid solvent replica exchange simulations with NAMD. We will also add here any news on new projects and applications for our methods. TIGER2h(s)_PE is an optimized REMD derivative allowing enhanced sampling MD simulations to sample protein folding, protein-protein interactions, protein structure refinements, and protein conformational dynamics. It offers to select the number of replicas independent from the system size and can effectively be used on any hardware NAMD can run on. With sufficiant resources, however, REMD simulations of huge systems can be efficiently realized to explore the conformational space of biological systems of unseen complexity.

Usage

Setup a NAMD simulation with TIGER2hs_PE for one of the example system (AAQAA, HP7, TrpCage):

#copy files
cp -r <Repository Path>/systems/<system> simulation & cd simulation
cp -r <Repository Path>/src/TIGER2hs_PE remd
cp -r <Repository Path>/tools .
cp remd/template.sh simulation.sh

Edit the simulation.sh and add values according to system's README. Then run the simulation:

./simulation.sh

You can monitor the sampling and exchange process by get_samping.tcl and exmat.tcl:

./tools/exmat.tcl
./remd/get_sampling.tcl <timestep>

Further information see: Tutorial

Required software

We normally run our simulations with an MPI built of NAMD-2.13 or later. Our implementations work fine with CUDA enabled NAMD builts. Launch options in template.sh may need updates for charmrun and specialized compute clusters. The hybrid solvent energy is now generated by OpenMM and MDAnalysis and hence requires a python 3.7 environment with these packages installed.

TODO

• Add parameters to choose between wrapped or unwrapped output for hybrid solvent state
• Add option to write the trajectory for all replicas, not only the baseline

Cite this work

Fundamental Redesign of the TIGER2hs Kernel to Address Severe Parameter Sensitivity
Lukas Schulig, Norman Geist, Mihaela Delcea, Andreas Link, and Martin Kulke
Journal of Chemical Information and Modeling
DOI: 10.1021/acs.jcim.2c00476

See also

• Fundamental Redesign of the TIGER2hs Kernel to Address Severe Parameter Sensitivity
• Replica-Based Protein Structure Sampling Methods II: Advanced Hybrid Solvent TIGER2hs
• Replica-Based Protein Structure Sampling Methods: Compromising between Explicit and Implicit Solvents
• TIGER2 with solvent energy averaging (TIGER2A): An accelerated sampling method for large molecular systems with explicit representation of solvent
• TIGER2: An improved algorithm for temperature intervals with global exchange of replicas
• An improved replica-exchange sampling method: Temperature intervals with global energy reassignment

Applications

• Biochemical analyses of cystatin-C dimers and cathepsin-B reveals a trypsin-driven feedback mechanism in acute pancreatitis
• Double the Double: Revisiting BCL11B's Multimerization
• Acetyl-CoA synthetase activity is enzymatically regulated by lysine acetylation using acetyl-CoA or acetyl-phosphate as donor molecule
• Bioinspired Genetic and Chemical Engineering of Protein Hydrogels for programable Multi-responsive Actuation
• Characterization of promoter elements of isoprene-responsive genes and the ability of isoprene to bind START domain transcription factors
• Molecular interplay of ADAMTS13-MDTCS and von willebrand Factor-A2: deepened insights from extensive atomistic simulations
• Molecular Design and Preparation of Protein-Based Soft Ionic Conductors with Tunable Properties
• Thermo- and ion-responsive silk-elastin-like proteins and their multiscale mechanisms
• Identification of a HTT-specific binding motif in DNAJB1 essential for suppression and disaggregation of HTT
• A Hypothesized Mechanism for Chronic Pancreatitis Caused by the N34S Mutation of Serine Protease Inhibitor Kazal-Type 1 Based on Conformational Studies
• Nuclear import of BCL11B is mediated by a classical nuclear localization signal and not the Krüppel-like zinc fingers
• Birefringent Silk Fibroin Hydrogel Constructed via Binary Solvent-Exchange-Induced Self-Assembly
• Unveiling the N-Terminal Homodimerization of BCL11B by Hybrid Solvent Replica-Exchange Simulations
• Phosphorylation of fibronectin influences the structural stability of the predicted interchain domain
• Effect of the silica nanoparticle size on the osteoinduction of biomineralized silk-silica nanocomposites