Iterative Landmark-Based Umbrella Sampling (ILBUS) Protocol for Sampling of Conformational Space of Biomolecules

0562066 - ÚOCHB 2023 RIV US eng J - Journal Article
Vymětal, Jiří - Vondrášek, Jiří
Iterative Landmark-Based Umbrella Sampling (ILBUS) Protocol for Sampling of Conformational Space of Biomolecules.
Journal of Chemical Information and Modeling. Roč. 62, č. 19 (2022), s. 4783-4798. ISSN 1549-9596. E-ISSN 1549-960X
R&D Projects: GA ČR(CZ) GA19-03488S; GA MŠMT(CZ) EF16_019/0000729
Research Infrastructure: e-INFRA CZ - 90140
Institutional support: RVO:61388963
Keywords : Monte-carlo simulation * molecular dynamics * alanine dipeptidea
OECD category: Biochemistry and molecular biology
Impact factor: 5.6, year: 2022
Method of publishing: Limited access
https://doi.org/10.1021/acs.jcim.2c00370

Computer simulations of biomolecules such as molecular dynamics often suffer from insufficient sampling. Due to limited computational resources, insufficient sampling prevents obtaining proper equilibrium distributions of observed properties. To deal with this problem, we proposed a simulation protocol for efficient resampling of collected off-equilibrium trajectories. These trajectories are utilized for the initial mapping of the conformational space, which is later properly resampled by the introduced Iterative Landmark-Based Umbrella Sampling (ILBUS) method. Reconstruction of static equilibrium properties is achieved by the multistate Bennett acceptance ratio (MBAR) method, which enables efficient use of simulated data. The ILBUS protocol is geometry-based and does not demand any additional collective variable or a dimensional-reduction technique. The only requirement is a set of suitably spaced reference conformations, which serve as landmarks in the mapped conformational space. Additionally, the ILBUS protocol encompasses an iterative process that optimizes the force constant used in the umbrella sampling simulation. Such tuning is an inherent feature of the protocol and does not need to be performed by the user in advance. Furthermore, even the simulations with suboptimal force constants can be used in estimates by MBAR. We demonstrate the feasibility and the performance of this approach in the study of the conformational landscape of the alanine dipeptide, met-enkephalin, and adenylate kinase.
Permanent Link: https://hdl.handle.net/11104/0334483