Application of network thermodynamics to the computer modeling of the pharmacology of anticancer agents: a network model for methotrexate action as a comprehensive example.
Application of network thermodynamics to the computer modeling of the pharmacology of anticancer agents: a network model for methotrexate action as a comprehensive example.
复制标题
网络热力学在抗癌药药理学计算机建模中的应用：甲氨蝶呤作用的网络模型作为综合示例。
DOI：
10.1016/0163-7258(81)90045-0
复制
发表时间：
1981
影响因子：
13.5
通讯作者：
D. Mikulecky
中科院分区：
文献类型：
--
作者：
J. White;D. Mikulecky
要彻底了解化疗药物给药的药理学后果，需要研究药物与其靶部位、单细胞、选定组织和整个身体的相互作用。应同时考虑所有现有信息。然而，即使在分子水平上，药物的作用也可能过于复杂，无法简单地通过直觉准确解释。从许多可能相互矛盾的信息中预测药物暴露结果的问题的一个解决方案是使用计算机模拟来衡量所有已知因素的重要性。利用网络热力学原理的计算机模拟将在这里介绍。网络热力学是研究相互依赖的流力关系的动力学的理论方法。流-力关系是大多数生物学研究的核心。流动物质的一些示例可以是分子、离子电荷或体积（主要是水），并且驱动这些流动的力的示例可以分别是化学势（例如跨膜浓度梯度）、电势（例如跨膜电势差）或压力。为了准备网络分析，将物料流动的路径表示为网络。代谢图是分子流动路线网络的一个很好的例子。由于涉及时间相关的事件，在这些流动过程中，必须考虑能量及其变化率，即功率。物质流动的方向始终符合热力学定律。这些定律要求由力的施加产生的流动发生在导致驱动力减小的方向上。对于独立的过程，流动将总是“下坡”走向平衡;代谢反应自发地减少，等等。唯一的例外是当两个或多个过程相互作用时，一个或多个过程可以提供动力来驱动其他过程。对于这些耦合过程，可以建立浓度梯度，并保持远离平衡的代谢能量为代价，在主动运输。大的、高度组织化的大分子可以以其他分子的降解为代价来合成，例如作为燃料的葡萄糖。依赖于时间的过程或瞬态，最终导致达到平衡态或远离平衡的稳态，这取决于系统的结构和实验条件。生物学家感兴趣的流和力通常是相互耦合的，这样他们就可以建立或维持组织，而代价是新陈代谢的能量输入。这导致了一些非常复杂的
A thorough understanding of the pharmacologic consequences of the administration of chemotherapeutic agents requires investigation of drug interactions with its target site, single cell, selected tissues and the body as a whole. All of the available information should be considered simultaneously. However, even at the molecular level drug effects may be too complex to be interpreted accurately simply by intuition. One solution to the problem of predicting the results of drug exposure from many pieces of possibly conflicting information has been to use computer simulation to weigh the importance of all known factors. Computer simulation utilizing the principles of network thermodynamics will be presented here.Network thermodynamics is a theoretical approach for investigating the dynamics of interdependent flow-force relationships. Flow-force relationships are at the heart of most biological research. Some examples of flowing material might be molecules, ionic charge or volume (mainly water) and examples of forces driving these flows might be chemical potential (eg transmembrane concentration gradients), electrical potential (eg transmembrane electrical potential difference) or pressure, respectively. To prepare for a network analysis the pathways through which materials flow are represented as a network. A metabolic chart is a good example of a network of routes for flow of molecules. Since time-dependent events are involved, both energy and its rate of change, power, must be considered in these flow processes. The direction in which materials flow will always be consistent with the laws of thermodynamics. These laws require that the flow resulting from application of a force occurs in the direction that results in reduction of the driving force. The flow will always be'downhill'towards equilibrium for independent processes; metabolic reactions spontaneously diminish, etc. The only way there can be an exception to this is when two or more processes interact in such a way that one or more can supply power to drive the others. For these coupled processes, concentration gradients can be built and maintained away from equilibrium at the expense of metabolic energy as in active transport. Large, highly organized macromolecules can be synthesized at the expense of the degradation of others, such as glucose, which act as fuel. Time-dependent processes, or transients, lead ultimately to the achievement of either equilibrium states or steady states away from equilibrium, depending on the way the system is structed and the experimental conditions. The flows and forces of interest to biologists are often coupled to one another so that they can build or maintain organization at the expense of power input from metabolism. This leads to some very complex
所有 L1210 细胞系中的甲氨蝶呤耐药性是由于二氢叶酸还原酶增加、胸苷酸合成酶活性降低和膜转运正常所致。
DOI：
--
发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
White,JC;Goldman,ID
通讯作者：
Goldman,ID