<scp>CAN</scp>: A new program to streamline preparation of molecular coordinate files for molecular dynamics simulations

A., Parkman, Jacob; Barksdale, Caleb A.; Michaelis, David J.

doi:10.1002/jcc.26729

Cited by 3 publications

(4 citation statements)

References 25 publications

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“…Our first MD approach uses a classic sampling method by starting with a linear conformation of the peptide backbone and allowing the system to evolve naturally over time. We used our previously reported CAN program to build coordinate files, including for catalyst-containing non-natural amino acids . We then heated the system above 500 K, allowed the system to cool, and then ran the simulation at the target temperature (273 K).…”

Section: Resultsmentioning

confidence: 99%

Structural Analysis of Non-native Peptide-Based Catalysts Using 2D NMR-Guided MD Simulations

Parkman,

Barlow,

Sheppert

et al. 2023

J. Phys. Chem. A

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Proteins and enzymes generally achieve their functions by creating well-defined 3D architectures that preorganize reactive functionalities. Mimicking this approach to supramolecular pre-organization is leading to the development of highly versatile artificial chemical environments, including new biomaterials, medicines, artificial enzymes, and enzyme-like catalysts. The use of β-turn and α-helical motifs is one approach that enables the precise placement of reactive functional groups to enable selective substrate activation and reactivity/selectivity that approaches natural enzymes. Our recent work has demonstrated that helical peptides can serve as scaffolds for pre-organizing two reactive groups to achieve enzyme-like catalysis. In this study, we used CYANA and AmberTools to develop a computational approach for determining how the structure of our peptide catalysts can lead to enhancements in reactivity. These results support our hypothesis that the bifunctional nature of the peptide enables catalysis by pre-organizing the two catalysts in reactive conformations that accelerate catalysis by proximity. We also present evidence that the low reactivity of monofunctional peptides can be attributed to interactions between the peptide-bound catalyst and the helical backbone, which are not observed in the bifunctional peptide.

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Section: Resultsmentioning

confidence: 99%

Structural Analysis of Non-native Peptide-Based Catalysts Using 2D NMR-Guided MD Simulations

Parkman,

Barlow,

Sheppert

et al. 2023

J. Phys. Chem. A

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“…The first step helps introduce the physics model, solvents, and other molecules that are going to define the system. Tools such as Charmm-GUI and others , facilitate this interconversion , from an initial structure to the generation of the simulation system. However, not everything is accounted for; for example, SARS-CoV-2 exposed many expert groups the challenges in modeling glycans into proteins, which lead to new protocols introduced in these pipelines.…”

Section: Lack Of Interoperability Across MD Platforms Requires More I...mentioning

confidence: 99%

Advancing Molecular Dynamics: Toward Standardization, Integration, and Data Accessibility in Structural Biology

Caparotta,

Perez

2024

J. Phys. Chem. B

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Molecular dynamics (MD) simulations have become a valuable tool in structural biology, offering insights into complex biological systems that are difficult to obtain through experimental techniques alone. The lack of available data sets and structures in most published computational work has limited other researchers' use of these models. In recent years, the emergence of online sharing platforms and MD database initiatives favor the deposition of ensembles and structures to accompany publications, favoring reuse of the data sets. However, the lack of uniform metadata collection, formats, and what data are deposited limits the impact and its use by different communities that are not necessarily experts in MD. This Perspective highlights the need for standardization and better resource sharing for processing and interpreting MD simulation results, akin to efforts in other areas of structural biology. As the field moves forward, we will see an increase in popularity and benefits of MD-based integrative approaches combining experimental data and simulations through probabilistic reasoning, but these too are limited by uniformity in experimental data availability and choices on how the data are modeled that are not trivial to decipher from papers. Other fields have addressed similar challenges comprehensively by establishing task forces with different degrees of success. The large scope and number of communities to represent the breadth of types of MD simulations complicates a parallel approach that would fit all. Thus, each group typically decides what data and which format to upload on servers like Zenodo. Uploading data with FAIR (findable, accessible, interoperable, reusable) principles in mind including optimal metadata collection will make the data more accessible and actionable by the community. Such a wealth of simulation data will foster method development and infrastructure advancements, thus propelling the field forward.

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“…17 We used our recently developed CAN program to build coordinate files that included catalystcontaining non-natural amino acids. 18 The MD structure is shown in Figure 3c and displays significant helical character. This structure was run on the Duke University MolProbity web server 19 and received a score in the 100th percentile, which suggests a reasonable MD structure (see the Supporting Information for details).…”

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confidence: 99%

“…We also performed an NOE-restrained MD simulation of peptide p11 using Ambertools . We used our recently developed CAN program to build coordinate files that included catalyst-containing non-natural amino acids . The MD structure is shown in Figure c and displays significant helical character.…”

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confidence: 99%

Optimizing the Local Chemical Environment on a Bifunctional Helical Peptide Scaffold Enables Enhanced Enantioselectivity and Cooperative Catalysis

et al. 2022

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We describe a proof-of-concept study in which peptide-bound enamine and thiourea catalysts are used to facilitate the conjugate addition of cyclohexanone to nitroolefins. Our bifunctional peptide scaffold is modified to optimize the local environment around both catalysts to enhance both reactivity and enantioselectivity, affording selectivities of ≤95% ee. Circular dichroism, nuclear magnetic resonance nuclear Overhauser effect studies, and molecular dynamics simulations verify the helical structure of our catalyst in solution and the importance of the secondary structure in catalysis.

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CAN: A new program to streamline preparation of molecular coordinate files for molecular dynamics simulations

Cited by 3 publications

References 25 publications

Structural Analysis of Non-native Peptide-Based Catalysts Using 2D NMR-Guided MD Simulations

Structural Analysis of Non-native Peptide-Based Catalysts Using 2D NMR-Guided MD Simulations

Advancing Molecular Dynamics: Toward Standardization, Integration, and Data Accessibility in Structural Biology

Optimizing the Local Chemical Environment on a Bifunctional Helical Peptide Scaffold Enables Enhanced Enantioselectivity and Cooperative Catalysis

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