Hybrid Models and Biological Model Reduction with PyDSTool

The PyDSTool software environment is designed to develop, simulate, and analyze dynamical systems models, particularly for biological applications. Unlike the engineering application focus and graphical specification environments of most general purpose simulation tools, PyDSTool provides a programmatic environment well suited to exploratory data- and hypothesis-driven biological modeling problems. In this work, we show how the environment facilitates the application of hybrid dynamical modeling to the reverse engineering of complex biophysical dynamics; in this case, of an excitable membrane. The example demonstrates how the software provides novel tools that support the inference and validation of mechanistic hypotheses and the inclusion of data constraints in both quantitative and qualitative ways. The biophysical application is broadly relevant to models in the biosciences. The open source and platform-independent PyDSTool package is freely available under the BSD license from http://sourceforge.net/projects/pydstool/. The hosting service provides links to documentation and online forums for user support.     

Development of a Prototype System for Archiving Integrative/Hybrid Structure Models of Biological Macromolecules

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Single Macromolecules: Hierarchic Thermodynamics, Irreversibility and Biological Function

Single homo-polymers show two different paths in the folding transition; a liquid-like spherical globule is generated for flexible polymers, whereas a rich variety of ordered structures are formed for semi-flexible polymers. This unique characteristic is discussed in relation to its biological significance.     

Diffusive Dynamics in a Detailed Potential: Application to Biological Macromolecules

Abstract

The local dynamics of macromolecules is obtained to second-order in the mode-coupling expansion of the Smoluchowski diffusion theory. The NMR spin-lattice relaxation times of different ¹³C or ¹⁵N nuclei along the chains are calculated and compared to experimental data from the literature. The macromolecules are considered as fluctuating 3D structures undergoing rotational diffusion. The fluctuations can be evaluated with any technique for sampling the configurational space. In the presented test cases Molecular Dynamics simulations have been applied to a DNA fragment and to the NK-2 homeodomain. In the case of the double-stranded DNA fragment d(TpCpGpCpG)₂, second and even first order theories are found to be in close agreement with experimental results. The major advantage of the diffusion technique is that only a good statistics is important as input while the solvent dynamic effects enter through hydrodynamic theory. Application based on Hybrid Monte Carlo schemes coupled with J-walking, are now in progress.     

贝类生物矿化中的生物大分子与分子识别

综述了贝类生物矿化相关的生物大分子性质及其分子识别过程的最新研究进展.生物矿化原理为仿生材料科学和分子构造学提供了崭新的思路.贝类生物矿化过程是生物大分子指导无机晶体的晶核形成、定向及生长的过程,是有机相-无机相、无机相-无机相界面分子识别的过程.     

Modeling Complex Phenotypes: Generalized Linear Models Using Spectrogram Predictors of Animal Communication Signals

Summary A major goal of evolutionary biology is to understand the dynamics of natural selection within populations. The strength and direction of selection can be described by regressing relative fitness measurements on organismal traits of ecological significance. However, many important evolutionary characteristics of organisms are complex, and have correspondingly complex relationships to fitness. Secondary sexual characteristics such as mating displays are prime examples of complex traits with important consequences for reproductive success. Typically, researchers atomize sexual traits such as mating signals into a set of measurements including pitch and duration, in order to include them in a statistical analysis. However, these researcher‐defined measurements are unlikely to capture all of the relevant phenotypic variation, especially when the sources of selection are incompletely known. In order to accommodate this complexity we propose a Bayesian dimension‐reduced spectrogram generalized linear model that directly incorporates representations of the entire phenotype (one‐dimensional acoustic signal) into the model as a predictor while accounting for multiple sources of uncertainty. The first stage of dimension reduction is achieved by treating the spectrogram as an “image” and finding its corresponding empirical orthogonal functions. Subsequently, further dimension reduction is accomplished through model selection using stochastic search variable selection. Thus, the model we develop characterizes key aspects of the acoustic signal that influence sexual selection while alleviating the need to extract higher‐level signal traits a priori. This facet of our approach is fundamental and has the potential to provide additional biological insight, as is illustrated in our analysis.     

Dynamics of Biological Macromolecules: Not a Simple Slaving by Hydration Water

We studied the dynamics of hydrated tRNA using neutron and dielectric spectroscopy techniques. A comparison of our results with earlier data reveals that the dynamics of hydrated tRNA is slower and varies more strongly with temperature than the dynamics of hydrated proteins. At the same time, tRNA appears to have faster dynamics than DNA. We demonstrate that a similar difference appears in the dynamics of hydration water for these biomolecules. The results and analysis contradict the traditional view of slaved dynamics, which assumes that the dynamics of biological macromolecules just follows the dynamics of hydration water. Our results demonstrate that the dynamics of biological macromolecules and their hydration water depends strongly on the chemical and three-dimensional structures of the biomolecules. We conclude that the whole concept of slaving dynamics should be reconsidered, and that the mutual influence of biomolecules and their hydration water must be taken into account.     

分子动态模拟及其在生物大分子研究中的应用

生物分子动念模拟技术是运用计算机对生物大分子的结构、功能、质子运动轨迹以及生物分子间的相互作用进行预测,是研究生物分子结构和功能的重要手段.该文介绍分子动态技术的原理及其在生命科学研究中的应用和研究进展,分析目前存在的问题,并提出对未来工作的展望.     

太赫兹(THz)光谱在生物大分子研究中的应用

太赫兹(THz)辐射是一种新型的远红外相干辐射源,近年来,在生物大分子研究中得到了广泛的应用,特别是在生物分子的结构和动力学特性等方面有着巨大的应用潜力.结合THz光谱的特点,介绍了利用THz光谱对蛋白质、糖类及DNA等生物大分子的探索研究,以及THz技术在测定水环境与生物分子相互作用等方面的应用.探讨了该技术在生物学领域应用中有待解决的问题及发展前景.     

Projection Methods for the Analysis of Complex Motions in Macromolecules

Abstract

In studies of macromolecular dynamics it is often desirable to analyze complex motions in terms of a small number of coordinates. Only for simple types of motion, e.g., rigid-body motions, these coordinates can be easily constructed from the Cartesian atomic coordinates. This article presents an approach that is applicable to infinitesimal or approximately infinitesimal motions, e.g., Cartesian velocities, normal modes, or atomic fluctuations. The basic idea is to characterize the subspace of interesting motions by a set of (possibly linearly dependent) vectors describing elementary displacements, and then project the dynamics onto this subspace. Often the elementary displacements can be found by physical intuition. The restriction to small displacements facilitates the study of complicated coupled motions and permits the construction of collective-motion subspaces that do not correspond to any set of generalized coordinates.

As an example for this technique, we analyze the low-frequency normal modes of proteins up to ≈ 20 THz (600 cm^?1) in order to see what kinds of motions occupy which frequency range. This kind of analysis is useful for the interpretation of spectroscopic measurements on proteins, e.g., inelastic neutron scattering experiments.