Naslov
Multi-scale stochastic organization-oriented coarse-graining exemplified on the human mitotic checkpoint

Autori
Henze, Richard ; Mu, Chunyan ; Puljiz, Mate ; Kamaleson, Nishanthan ; Huwald, Jan ; Haslegrave, John ; di Fenizio, Pietro Speroni ; Parker, David ; Good, Christopher ; Rowe, Jonathan E. ; Ibrahim, Bashar ; Dittrich, Peter

Izvornik
Scientific Reports (2045-2322) 9 (2019), 1; 1-17

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
spindle assembly checkpoint ; coarse-graining methods

Sažetak
The complexity of biological models makes methods for their analysis and understanding highly desirable. Here, we demonstrate the orchestration of various novel coarse-graining methods by applying them to the mitotic spindle assembly checkpoint. We begin with a detailed fine-grained spatial model in which individual molecules are simulated moving and reacting in a three-dimensional space. A sequence of manual and automatic coarse-grainings finally leads to the coarsest deterministic and stochastic models containing only four molecular species and four states for each kinetochore, respectively. We are able to relate each more coarse-grained level to a finer one, which allows us to relate model parameters between coarse-grainings and which provides a more precise meaning for the elements of the more abstract models. Furthermore, we discuss how organizational coarse-graining can be applied to spatial dynamics by showing spatial organizations during mitotic checkpoint inactivation. We demonstrate how these models lead to insights if the model has different “meaningful” behaviors that differ in the set of (molecular) species. We conclude that understanding, modeling and analyzing complex biomolecular systems can greatly benefit from a set of coarse-graining methods that, ideally, can be automatically applied and that allow the different levels of abstraction to be related.

Izvorni jezik
Engleski

Znanstvena područja
Matematika

POVEZANOST RADA