Spatial Rule-Based Simulations: The SRSim Software.

SRSim combines rule-based reaction network models with spatial particle simulations allowing to simulate the dynamics of large molecular complexes changing according to a set of chemical reaction rules. As the rule can contain patterns of molecular complexes and specific states of certain binding sites, a combinatorially complex or even infinitely sized reaction network can be defined. Particles move in a three-dimensional space according to molecular dynamics implemented by LAMMPS, while the BioNetGen language is used to formulate reaction rules.

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

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 Dynamical Model for Activating and Silencing the Mitotic Checkpoint.

The spindle assembly checkpoint (SAC) is an evolutionarily conserved mechanism, exclusively sensitive to the states of kinetochores attached to microtubules. During metaphase, the anaphase-promoting complex/cyclosome (APC/C) is inhibited by the SAC but it rapidly switches to its active form following proper attachment of the final spindle. It had been thought that APC/C activity is an all-or-nothing response, but recent findings have demonstrated that it switches steadily.

Structural analysis of in silico mutant experiments of human inner-kinetochore structure.

Large multi-molecular complexes like the kinetochore are lacking of suitable methods to determine their spatial structure. Here, we use and evaluate a novel modeling approach that combines rule-bases reaction network models with spatial molecular geometries. In particular, we introduce a method that allows to study in silico the influence of single interactions (e.

Active transport can greatly enhance Cdc20:Mad2 formation.

To guarantee genomic integrity and viability, the cell must ensure proper distribution of the replicated chromosomes among the two daughter cells in mitosis.The mitotic spindle assembly checkpoint (SAC) is a central regulatory mechanism to achieve this goal. A dysfunction of this checkpoint may lead to aneuploidy and likely contributes to the development of cancer.

Spatial rule-based modeling: a method and its application to the human mitotic kinetochore.

A common problem in the analysis of biological systems is the combinatorial explosion that emerges from the complexity of multi-protein assemblies. Conventional formalisms, like differential equations, Boolean networks and Bayesian networks, are unsuitable for dealing with the combinatorial explosion, because they are designed for a restricted state space with fixed dimensionality. To overcome this problem, the rule-based modeling language, BioNetGen, and the spatial extension, SRSim, have been developed.

Surgical correction of a congenital coronary arterial fistula and a massive sinus of Valsalva aneurysm.

The case of a 22-year old male patient who presented with a congenital coronary arterial fistula from the right coronary artery to the right ventricle is described. The arterial fistula had led to an aneurysm of the right sinus of Valsalva and the proximal right coronary artery. The aneurysm was incised from the aorta and the fistula closed with a pericardial patch.

Beneficial effect of sodium nitroprusside after coronary artery bypass surgery: pump function correlates inversely with cardiac release of proinflammatory cytokines.

The authors studied the relationship between cardiac cytokine release and pump function and whether low-dose application of sodium nitroprusside (SNP) improves cardiac performance during coronary artery bypass graft (CABG) creation. Cardiac reperfusion and application of nitric oxide have an influence on cytokine release. However, the functional consequences are unclear.