A Multiscale Algorithm for Spatiotemporal Modeling of Multivalent Protein-Protein Interaction.
J Comput Biol
; 24(12): 1275-1283, 2017 Dec.
Article
en En
| MEDLINE
| ID: mdl-29099235
ABSTRACT
This article introduces a multiscale framework for spatiotemporal modeling of protein-protein interaction. Cellular protein molecules represent multivalent species that contain modular features, such as binding domains and phosphorylation motifs. The binding and transformations of these features occur at a small time and spatial scale. On the other hand, space and time involved in protein diffusion, colocalization, and formation of complexes could be relatively large. Here, we present an agent-based framework integrated with a multiscale Brownian Dynamics (BD) simulation algorithm. The framework employs spatial graphs to describe multivalent molecules and complexes with their site-specific details. By implementing a time-adaptive feature, the BD algorithm enables efficient computation while capturing the site-specific interactions of the diffusing species at the sub-nanometer scale. We demonstrate these capabilities by modeling two multivalent molecules, one representing a ligand and the other a receptor, in a two-dimensional plane (cell membrane). Using the model, we show that the algorithm can accelerate computation by orders of magnitudes in both concentrated and dilute regimes. We also show that the algorithm enables robust model predictions against a wide range of selection of time step sizes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Algoritmos
/
Proteínas
/
Mapas de Interacción de Proteínas
/
Análisis Espacio-Temporal
/
Modelos Teóricos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Comput Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
INFORMATICA MEDICA
Año:
2017
Tipo del documento:
Article