# Theory—New Methods—Parallel Computation

#### Three-Photon Correlations

The main challenges of single molecule scattering experiments are the unknown random orientation of the molecule in each shot and the extremely low signal to noise ratio due to the very low expected photon count per scattering image, typically well below the number of over 100 photons required by available analysis methods. Photon correlations are a summary statistic of the scattering images that...

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### SESCA: Semi-Empirical-Spectrum-Calculation-Algorithm

SESCA is a computational method that allows the rapid and accurate prediction of the CD spectra of protein models from their three-dimensional structure. SESCA predictions are based on two things: the secondary structure composition of the proposed protein models, and a set of pre-calculated basis spectra (basis set). SESCA calculations allow a direct comparison between the measured CD spectrum of a target protein and predicted CD spectra based a model structures or structural ensembles for determining the model quality.

[more]### GROMACS molecular dynamics simulations

Simulations of big molecular dynamics systems can easily occupy a compute cluster for weeks or even months. Continuous efforts are being made to ensure that our computing power is used most efficiently. This includes network fine-tuning and code optimizations to reach the best possible parallel scaling. [more]

### IDP Force Field Development

Intrinsically disordered proteins (IDPs) are notoriously challenging to study both experimentally and computationally. Our findings highlight how IDPs, with their rugged energy landscapes, are highly sensitive test systems that are capable of revealing force field deficiencies and, therefore, contributing to force field development.

[more]### NuSol - Solving the Schrödinger Equation for the Protein Nuclei

Molecular dynamics simulations as well as most quantum classical QM/MM simulations treat the nuclei of the protein atoms as classical particles. Under physiological conditions (room temperature), quantum effects of the atomic nuclei can largely be neglected. It is only under special conditions, that these effects become important and have to be considered beyond the classical nuclei approximation.

[more]### Cryo-EM correlation-based fitting in GROMACS

A method for automated refinement of atomistic models into cryo-electron (cryo-EM) maps. [more]

### Unified Long-Range Electrostatics and Dynamic Protonation for Realistic Biomolecular Simulations on the Exascale

As a project within the DFG Exascale SPP, we target a flexible and portable exascale algorithm for potentials and forces, a prerequisite for exascale applications in particle-based simulations with long-range interactions in general.

[more]### CGI – Accurate Free Energy Differences from Non-Equilibrium Simulations

The molecular-dynamics-based calculation of accurate free energy differences for biomolecular systems is a challenging task. We suggest and assess a new nonequilibrium free energy method, Crooks Gaussian Intersection (CGI), which combines the advantages of existing methods.

[more]### Predicting Unimolecular Chemical Reactions: Chemical Flooding

The calculation of reaction pathways, energy barriers and reaction rates for chemical reactions of small molecules is a routine task in todays theoretical quantum chemistry. Established methods exist for tasks like (a) minimization of educt states, (b) exploring potential energy hypersurfaces, (c) detecting transition and product states, (d) finding reaction pathways connecting the educt, ...

[more]### Predicting Conformational Transitions: Conformational Flooding

We present a method to predict complex structural (conformational) transitions in irregular or disordered macromolecular systems, such as proteins or glasses, at the atomic level. Our method aims at rare events, which currently cannot be predicted with traditional molecular dynamics (MD) simulations, since these currently are limited to time scales shorter than a few nanoseconds. ...

[more]### Conformational Dynamics of Proteins

Proteins are polypeptides which consist of typically 50 to several 100 amino acids and fold into protein-specific three-dimensional structures. This native structure is determined by the amino acid sequence of a protein, which is genetically encoded.

[more]### Charting Protein Dynamics Space: The Dynasome

We have developed a comprehensive dynamics space for protein dynamics based on 34 observables that can be obtained from molecular dynamics simulation. Distances in this space serve as a measure for protein dynamics similarity which, in turn, allows to quantify structure-dynamics and dynamics-function relationships.

[more]### Constant pH Molecular Dynamics Simulations

Typically, in a molecular dynamics simulation, the protonation states of ionizable groups of a protein are set in the beginning of the simulation. This is not always an obvious task, in particular for histidine, as its pKa is close to the physiological pH. In contrast, in a constant pH molecular dynamics simulation, the protonation state of an ionizable group of a protein ... [more]

### CuTLat

Cutlat determines inter-repeat curvature, twist and lateral bending angles, as well as their full-length sums for multi-repeat unit proteins, including e.g. LRR, Armadillo, HEAT or ankyrin repeat proteins. As the principal axes of repeats are used for the calculation of inter-repeat angles, a prior selection of specific conserved reference groups is not required. ...

[more]### Theory of Dynamic Force Spectroscopy

Recent advances in atomic force microscopy, biomembrane force probe experiments, and optical tweezers allow to measure the response of single molecules to mechanical stress with high precision. Such experiments, due to limited spatial resolution, typically access only one single force value in a continuous force profile that characterizes the molecular response along ...

[more]### Flooding in Gromacs: Accelerated Barrier Crossings in Molecular Dynamics

The major bottleneck of today's atomistic molecular dynamics (MD) simulations is that due to the enormous computational effort involved only processes at nanoseconds to microseconds time scales or faster can be studied directly. Unfortunately, apart from a few expections, relevant processes, such as chemical reactions or many large-scale conformational motions ...

[more]### Full Correlation Analysis of Conformational Protein Dynamics

Collective coordinates for protein motions, can be extracted from MD simulations with established methods, mainly via calculation of the covariance matrix and subsequent principal component analysis[1]. This established approach, however, relies on quasi-harmonic treatment of the configurational ensemble and, therefore, detects only linearly correlated motions. ...

[more]### g_permute

Biomolecular processes are governed by free energy changes and thus depend on a fine-tuned interplay between entropy and enthalpy. To calculate accurate values for entropies from simulations is particularly challenging for the solvation shell of proteins, which contribute crucially to the total entropy of solvated proteins, due to the diffusive motion of the solvent ...

[more]### Generalized Correlation for Biomolecular Dynamics

Correlated motions in biomolecules, in particular proteins, are ubiquitous and often essential for biomolecular function. Correct assessment of correlated motions, both experimentally and from theory and simulations, is therefore crucial for a quantitative understanding of biomolecular function. The accurate characterization of correlated motions would also improve ...

[more]### Interactive Molecular Dynamics with GROMACS

Interactive Molecular Dynamics (IMD) allows users to monitor and interact with a running Molecular Dynamics (MD) simulation. To achive this with the GROMACS package, we provide a patched version, which allows running of interactive simulations by implementing the interactive molecular dynamics (IMD) protocol into GROMACS. The user then can interact with the simulation by pulling on atoms, residues or fragments with a mouse or force-feedback devices.

[more]### Flexible Axis Enforced Rotation

We describe a novel method to enforce rotation of a protein subunit in molecular dynamics (MD) simulations. Our »flexible axis« approach allows flexible adaptions of both the rotating subunit as well as the rotation axis during the simulation. For the example of F

[more]_{1}-ATP synthase we show that the flexible method (apart from the rotation itself) imposes minimal constraints ...### Solvate

Solvate is a program to construct an atomic solvent environment model for a given atomic macromolecule for the use in an MD simulation. Solvate generates irregularly-shaped solvent volumes, adapted to a given solute's structure. It allows efficient computation of boundary forces as required in molecular dynamics simulations.

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