使用 Molegro 虚拟 Docker 针对 CDK9 的目标.
1Department of Physics, Institute of Exact Sciences, Federal University of Alfenas, Alfenas, MG, Brazil.
Methods in molecular biology (Clifton, N.J.)
|October 11, 2025
概括
本研究介绍了一种机器学习工作流程,用于预测循环素依赖性激酶9 (CDK9) 抑制. 该方法整合了对接模拟和回归建模,以加强针对癌症的药物发现.
科学领域:
- 计算化学是一种计算化学.
- 生物信息学是一种生物信息学.
- 机器学习在药物发现中的作用
背景情况:
- 预测蛋白质 - 配体结合的亲和力对于药物发现至关重要.
- 在对接程序中的经典评分函数在预测性能上有局限性.
- 循环素依赖性激酶9 (CDK9) 是抗癌药物的潜在治疗标.
研究的目的:
- 开发和介绍一个工作流来构建一个神经网络模型来预测CDK9.9的抑制.
- 整合计算工具,以加强对得分函数空间的探索.
- 为了促进对CDK9抑制的有效回归模型的识别.
主要方法:
- 使用Molegro虚拟端口 (MVD) 进行对接模拟,能源计算和描述器生成.
- 雇佣了Molegro数据建模器 (MDM) 来使用MVD衍生功能的回归模型.
- 集成的MVD和MDM与Jupyter笔记本电脑,以简化工作流程.
- 来自BindingDB的结合亲和力数据和来自蛋白质数据库的蛋白质结构.
主要成果:
- 演示了一种结合MVD,MDM和Jupyter笔记本的工作流程,用于CDK9抑制预测.
- 成功构建了一个神经网络回归模型,用于预测CDK9抑制.
- 促进了评分函数空间的综合探索,以确定最佳的回归模型.
结论:
- 本工作流提供了一种可靠的方法来预测蛋白质-连接体结合亲和力,特别是对于CDK9.
- 这种综合计算策略提高了针对CDK9.9的潜在抗癌药物候选者的有效性.
- 开发的模型和数据集在GitHub上公开提供,以便进一步研究和应用.
相关概念视频
02:34Inhibition of Cdk Activity
5.5K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K
02:15M-Cdk Drives Transition Into Mitosis
6.2K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.2K
02:39Positive Regulator Molecules
6.4K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
6.4K
02:38S-Cdk Initiates DNA Replication
5.3K
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
5.3K
02:57Targeted Cancer Therapies
8.6K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
8.6K