Allosteric Modulation of Thrombin by Thrombomodulin: Insights from Logistic Regression and Statistical Analysis of Molecular Dynamics Simulations.

Thrombomodulin (TM), a transmembrane receptor integral to the anticoagulant pathway, governs thrombin's substrate specificity via interaction with thrombin's anion-binding exosite I. Despite its established role, the precise mechanisms underlying this regulatory function are yet to be fully unraveled. In this study, we deepen the understanding of these mechanisms through eight independent 1 μs all-atom simulations, analyzing thrombin both in its free form and when bound to TM fragments TM456 and TM56.

Thrombin - A Molecular Dynamics Perspective.

Thrombin is a crucial enzyme involved in blood coagulation, essential for maintaining circulatory system integrity and preventing excessive bleeding. However, thrombin is also implicated in pathological conditions such as thrombosis and cancer. Despite the application of various experimental techniques, including X-ray crystallography, NMR spectroscopy, and HDXMS, none of these methods can precisely detect thrombin's dynamics and conformational ensembles at high spatial and temporal resolution.

Unraveling the Role of Hydrogen Bonds in Thrombin via Two Machine Learning Methods.

Hydrogen bonds play a critical role in the folding and stability of proteins, such as proteins and nucleic acids, by providing strong and directional interactions. They help to maintain the secondary and 3D structure of proteins, and structural changes in these molecules often result from the formation or breaking of hydrogen bonds. To gain insights into these hydrogen bonding networks, we applied two machine learning models - a logistic regression model and a decision tree model - to study four variants of thrombin: wild-type, ΔK9, E8K, and R4A.

Simulations suggest double sodium binding induces unexpected conformational changes in thrombin.

Thrombin is a Na[Formula: see text]-activated serine protease existing in two forms targeted to procoagulant and anticoagulant activities, respectively. There is one Na[Formula: see text]-binding site that has been the focus of the study of the thrombin. However, molecular dynamics (MD) simulations suggest that there might be actually two Na[Formula: see text]-binding sites in thrombin and that Na[Formula: see text] ions can even bind to two sites simultaneously.

Light Chain Mutation Effects on the Dynamics of Thrombin.

Thrombin plays an important role in the process of hemostasis and blood coagulation. Studies in thrombin can help us find ways to treat cancer because thrombin is able to reduce the characteristic hypercoagulability of cancer. Thrombin is composed of two chains, the light chain and the heavy chain.