Dataset Information

Modeling biomolecular kinetics with large-scale simulation.

ABSTRACT: The molecular details of biomolecular kinetics present a challenging estimation problem because the identities of relevant intermediates and the rates of exchange between them must be determined. These can be derived from prior knowledge, but in recent years, great advances have been made in the development and application of methods to systematically determine states and rates using biomolecular simulation. Doing this for biological systems of reasonable complexity requires substantial computational power, and contemporary methods leverage distributed computing or leadership-class computing resources to accomplish this. The result has been substantial insight into pressing contemporary problems, including structural activation of pandemic viruses. Here, we highlight recent developments in both methodology and exciting applications.

SUBMITTER: Kasson PM

PROVIDER: S-EPMC9476681 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Modeling biomolecular kinetics with large-scale simulation.

Kasson Peter M PM

Current opinion in structural biology 20210927

The molecular details of biomolecular kinetics present a challenging estimation problem because the identities of relevant intermediates and the rates of exchange between them must be determined. These can be derived from prior knowledge, but in recent years, great advances have been made in the development and application of methods to systematically determine states and rates using biomolecular simulation. Doing this for biological systems of reasonable complexity requires substantial computat ...[more]

PMID: 34592698

Similar Datasets

Project description:BACKGROUND: Molecular dynamics (MD) simulations provide valuable insight into biomolecular systems at the atomic level. Notwithstanding the ever-increasing power of high performance computers current MD simulations face several challenges: the fastest atomic movements require time steps of a few femtoseconds which are small compared to biomolecular relevant timescales of milliseconds or even seconds for large conformational motions. At the same time, scalability to a large number of cores is limited mostly due to long-range interactions. An appealing alternative to atomic-level simulations is coarse-graining the resolution of the system or reducing the complexity of the Hamiltonian to improve sampling while decreasing computational costs. Native structure-based models, also called G?-type models, are based on energy landscape theory and the principle of minimal frustration. They have been tremendously successful in explaining fundamental questions of, e.g., protein folding, RNA folding or protein function. At the same time, they are computationally sufficiently inexpensive to run complex simulations on smaller computing systems or even commodity hardware. Still, their setup and evaluation is quite complex even though sophisticated software packages support their realization. RESULTS: Here, we establish an efficient infrastructure for native structure-based models to support the community and enable high-throughput simulations on remote computing resources via GridBeans and UNICORE middleware. This infrastructure organizes the setup of such simulations resulting in increased comparability of simulation results. At the same time, complete workflows for advanced simulation protocols can be established and managed on remote resources by a graphical interface which increases reusability of protocols and additionally lowers the entry barrier into such simulations for, e.g., experimental scientists who want to compare their results against simulations. We demonstrate the power of this approach by illustrating it for protein folding simulations for a range of proteins. CONCLUSIONS: We present software enhancing the entire workflow for native structure-based simulations including exception-handling and evaluations. Extending the capability and improving the accessibility of existing simulation packages the software goes beyond the state of the art in the domain of biomolecular simulations. Thus we expect that it will stimulate more individuals from the community to employ more confidently modeling in their research.

Dataset Information

Modeling biomolecular kinetics with large-scale simulation.

Publications

Modeling biomolecular kinetics with large-scale simulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets