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Molecular dynamics simulations data of six compounds F3J-BRD4/CBP, EX1-BRD4/CBP, and E2T-BRD4/CBP.

ABSTRACT: The data here described are related to the research article entitled "Molecular dynamics insights into binding selectivity of inhibitors toward BRD4 and CBP" [1]. Bromodomain-containing protein 4 (BRD4) and CREB binding protein (CBP) play important roles in tumorigenesis and development. We performed 200-ns molecular dynamics (MD) simulations on three pairs of inhibitor-BRD4 and inhibitor-CBP complexes to clarify binding selectivity of inhibitors toward BRD4 and CBP. Principal component (PC) analysis was used to probe changes in internal dynamics and conformations of BRD4 and CBP due to inhibitor bindings. Analysis of residue-based free energy decomposition was employed to explore the roles of separate residues in binding selectivity of inhibitors to BRD4 versus CBP.

SUBMITTER: Wu S

PROVIDER: S-EPMC8058528 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Molecular dynamics simulations data of six compounds F3J-BRD4/CBP, EX1-BRD4/CBP, and E2T-BRD4/CBP.

Wu Shiliang S Wang Lifei L Zhang Lulu L Xu Xiaoyan X Zhao Juan J

Data in brief 20210327

The data here described are related to the research article entitled "Molecular dynamics insights into binding selectivity of inhibitors toward BRD4 and CBP" [1]. Bromodomain-containing protein 4 (BRD4) and CREB binding protein (CBP) play important roles in tumorigenesis and development. We performed 200-ns molecular dynamics (MD) simulations on three pairs of inhibitor-BRD4 and inhibitor-CBP complexes to clarify binding selectivity of inhibitors toward BRD4 and CBP. Principal component (PC) ana ...[more]

PMID: 33898668

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Project description:The blood-brain barrier (BBB) is formed by specialized tight junctions between endothelial cells that line brain capillaries to create a highly selective barrier between the brain and the rest of the body. A major problem to overcome in drug design is the ability of the compound in question to cross the BBB. Neuroactive drugs are required to cross the BBB to function. Conversely, drugs that target other parts of the body ideally should not cross the BBB to avoid possible psychotropic side effects. Thus, the task of predicting the BBB permeability of new compounds is of great importance. Two gold-standard experimental measures of BBB permeability are logBB (the concentration of drug in the brain divided by concentration in the blood) and logPS (permeability surface-area product). Both methods are time-consuming and expensive, and although logPS is considered the more informative measure, it is lower throughput and more resource intensive. With continual increases in computer power and improvements in molecular simulations, in silico methods may provide viable alternatives. Computational predictions of these two parameters for a sample of 12 small molecule compounds were performed. The potential of mean force for each compound through a 1,2-dioleoyl-sn-glycero-3-phosphocholine bilayer is determined by molecular dynamics simulations. This system setup is often used as a simple BBB mimetic. Additionally, one-dimensional position-dependent diffusion coefficients are calculated from the molecular dynamics trajectories. The diffusion coefficient is combined with the free energy landscape to calculate the effective permeability (Peff) for each sample compound. The relative values of these permeabilities are compared to experimentally determined logBB and logPS values. Our computational predictions correlate remarkably well with both logBB (R(2) = 0.94) and logPS (R(2) = 0.90). Thus, we have demonstrated that this approach may have the potential to provide reliable, quantitatively predictive BBB permeability, using a relatively quick, inexpensive method.

Dataset Information

Molecular dynamics simulations data of six compounds F3J-BRD4/CBP, EX1-BRD4/CBP, and E2T-BRD4/CBP.

Publications

Molecular dynamics simulations data of six compounds F3J-BRD4/CBP, EX1-BRD4/CBP, and E2T-BRD4/CBP.

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