File(s) not publicly available
Molecular simulation of conformational transitions in biomolecules using a combination of structure-based potential and empirical valence bond theory
journal contribution
posted on 2023-06-07, 22:48 authored by Giuseppe De Marco, Peter VarnaiThe functions of biological macromolecules are inherently linked to their complex conformational behaviour. As a consequence of this complexity, the corresponding potential energy landscapes encompass multiple minima. Some of the intermediate structures between initial and final states can be characterized by experimental techniques. Computer simulations can explore the dynamics of individual states and bring these together to rationalize the overall process. Here, we show that the experimental structures can be exploited to define simple yet accurate atomistic structure-based potentials (SBP) that describe individual conformational states. These individual states can then be coupled by using the empirical valence bond (EVB) model. The overall energy landscape can easily be parameterised to reproduce available kinetic and thermodynamic data. We illustrate the procedure by applying the EVB-SBP method to study base flipping in B-DNA. Simple SBP is shown to reproduce structural ensembles obtained by using more refined force field simulations. Umbrella sampling in conjunction with the general energy gap reaction coordinate enables us to study alternative molecular pathways efficiently. We find that base rotation takes place via both grooves of the B-DNA with a marked preference for the major groove pathway. We also identify an unusual high-energy off-pathway intermediate that may appear if the base closing process is initiated from a syn base.
History
Publication status
- Published
Journal
Physical Chemistry Chemical PhysicsISSN
1463-9076External DOI
Issue
45Volume
11Page range
10694-10700Pages
7.0Department affiliated with
- Chemistry Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC