Molecular Modeling

3。TR&D1 -摘要

III. TR&D1 - Abstract The last decade has seen the creation of a remarkably inventive array of approaches for 4D modeling of biomolecular systems, using coarse-grained models and enhanced-sampling methods, as well as spatiotemporally realistic approaches at cellular scale. However, “mesoscale” systems such as large multi-protein complexes and subcellular structures, and “omics-scale” systems like chromatin have received significantly less attention. There is a surging need to develop computational technology for structure-based mesoscopic- and spatially resolved omics-scale modeling. Several methodologies already developed by TR&D1 investigators show great promise for meeting this need. These include the methods and tools based on elastic network models (ENMs) and implemented in the ProDy Application Programming Interface (API) developed for modeling supramolecular systems dynamics, and the Armatus software developed for identifying topological associated domains in chromosomes. Our goal is to further develop these and other innovative technologies that we developed during the past term, such as weighted-ensemble (WE)-based methods and software (WESTPA) for enhancing simulation efficiency applicable to both molecular and cellular scales, toward addressing these newly emerging challenges. Our research and development activities will be driven by four Driving Biomedical Projects that will focus on the complex interactions controlling neurotransmission and neurosignaling events (DBP1-3), and on constructing a spatial dynamic map of transcription and chromatin structure (DBP6). We will work together with all three other TR&Ds to meet the multiscale challenges of the investigated complex systems and processes. Our aims are formulated as (1) advancing and implementing the methodology for treating the structure, dynamics, and interactions of multimeric proteins and multiprotein assemblies, (2) extending our computing capabilities to modeling chromosomal structure, dynamics and function, and (3) further development of TR&D1 high- performance computing (HPC) platform under the Bridges environment provided by the PSC, to ensure efficient integration of all software within TR&D1, as well as interoperability with those developed at the other three TR&Ds, and at other Resources pursuing complementary goals.