Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Chem Phys ; 128(20): 205101, 2008 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-18513044

RESUMO

The time evolution of species concentrations in biochemical reaction networks is often modeled using the stochastic simulation algorithm (SSA) [Gillespie, J. Phys. Chem. 81, 2340 (1977)]. The computational cost of the original SSA scaled linearly with the number of reactions in the network. Gibson and Bruck developed a logarithmic scaling version of the SSA which uses a priority queue or binary tree for more efficient reaction selection [Gibson and Bruck, J. Phys. Chem. A 104, 1876 (2000)]. More generally, this problem is one of dynamic discrete random variate generation which finds many uses in kinetic Monte Carlo and discrete event simulation. We present here a constant-time algorithm, whose cost is independent of the number of reactions, enabled by a slightly more complex underlying data structure. While applicable to kinetic Monte Carlo simulations in general, we describe the algorithm in the context of biochemical simulations and demonstrate its competitive performance on small- and medium-size networks, as well as its superior constant-time performance on very large networks, which are becoming necessary to represent the increasing complexity of biochemical data for pathways that mediate cell function.


Assuntos
Algoritmos , Modelos Químicos , Método de Monte Carlo , Cinética , Redes e Vias Metabólicas , Probabilidade , Processos Estocásticos , Fatores de Tempo
2.
Biophys J ; 85(4): 2213-23, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14507687

RESUMO

We extend our previous stochastic cellular automata-based model for two-dimensional (areal) aggregation of prion proteins on neuronal surfaces. The new anisotropic model allows us to simulate both strong beta-sheet and weaker attachment bonds between proteins. Constraining binding directions allows us to generate aggregate structures with the hexagonal lattice symmetry found in recently observed in vitro experiments. We argue that these constraints on rules may correspond to underlying steric constraints on the aggregation process. We find that monomer-dominated growth of the areal aggregate is too slow to account for some observed doubling-time-to-incubation-time ratios inferred from data, and so consider aggregation dominated by relatively stable but noninfectious oligomeric intermediates. We compare a kinetic theory analysis of oligomeric aggregation to spatially explicit simulations of the process. We find that with suitable rules for misfolding of oligomers, possibly due to water exclusion by the surrounding aggregate, the resulting oligomeric aggregation model maps onto our previous monomer aggregation model. Therefore it can produce some of the same attractive features for the description of prion incubation time data. We propose experiments to test the oligomeric aggregation model.


Assuntos
Biopolímeros/química , Cristalização/métodos , Dimerização , Modelos Químicos , Modelos Moleculares , Doenças Priônicas/metabolismo , Príons/química , Príons/metabolismo , Algoritmos , Animais , Sítios de Ligação , Simulação por Computador , Humanos , Substâncias Macromoleculares , Modelos Estatísticos , Ligação Proteica , Conformação Proteica , Estrutura Secundária de Proteína
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...