<i>ProDy</i> 2.0: increased scale and scope after 10 years of protein dynamics modelling with Python

Zhang, She; Krieger, James; Zhang, Yan; Kaya, Cihan; Kaynak, Burak; Mikulska-Ruminska, Karolina; Doruker, Pemra; Li, Hongchun; Bahar, İvet

doi:10.1093/bioinformatics/btab187

Cited by 114 publications

(86 citation statements)

References 19 publications

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“…The ClustENMD algorithm is implemented within ProDy ( Bakan et al , 2011 ; Zhang et al , 2021 ), an open-source Python API for protein structure, dynamics and sequence analysis, containing multiple modules. The ProDy package (downloaded more than 2.1 million times and visited by 140 000+ unique users worldwide) ensures broad dissemination of ClustENMD to the research community in addition to providing accessory tools for analyses and visualization.…”

Section: Discussionmentioning

confidence: 99%

“…Such promising results have motivated us to further develop and implement the ClustENMD version in the widely used ProDy ( Bakan et al , 2011 ; Zhang et al , 2021 ) application programming interface (API) via integration with OpenMM ( Eastman et al , 2017 ) software. This version allows us to generate more realistic conformers by performing short MD simulations even for large allosteric complexes, together with high efficiency and full automation within a Python environment.…”

Section: Introductionmentioning

confidence: 99%

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ClustENMD: efficient sampling of biomolecular conformational space at atomic resolution

et al. 2021

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Summary Efficient sampling of conformational space is essential for elucidating functional/allosteric mechanisms of proteins and generating ensembles of conformers for docking applications. However, unbiased sampling is still a challenge especially for highly flexible and/or large systems. To address this challenge, we describe a new implementation of our computationally efficient algorithm ClustENMD that is integrated with ProDy and OpenMM softwares. This hybrid method performs iterative cycles of conformer generation using elastic network model (ENM) for deformations along global modes, followed by clustering and short molecular dynamics (MD) simulations. ProDy framework enables full automation and analysis of generated conformers and visualization of their distributions in the essential subspace. Availability ClustENMD is open-source and freely available under MIT License from https://github.com/prody/ProDy. Supplementary information Supplementary materials comprising method details, figures, table and tutorial are available at Bioinformatics online.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ClustENMD: efficient sampling of biomolecular conformational space at atomic resolution

et al. 2021

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“…Simulations were performed with a cutoff of 12 Å for non-bonded interactions and Langevin piston algorithm to maintain the temperature at 300K and pressure at 1 atm. We used VMD [ 57 ] for visualization and ProDy [ 58 , 59 , 60 ] for trajectory analysis with in-house scripts. CAVER [ 61 ] 3.0 with PyMOL Molecular Graphics System, Version 1.8, Schrödinger, LLC was used to represent and display cavities and interior surfaces.…”

Section: Methodsmentioning

confidence: 99%

NO● Represses the Oxygenation of Arachidonoyl PE by 15LOX/PEBP1: Mechanism and Role in Ferroptosis

Mikulska-Ruminska

Anthonymuthu

Levkina

et al. 2021

IJMS

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We recently discovered an anti-ferroptotic mechanism inherent to M1 macrophages whereby high levels of NO● suppressed ferroptosis via inhibition of hydroperoxy-eicosatetraenoyl-phosphatidylethanolamine (HpETE-PE) production by 15-lipoxygenase (15LOX) complexed with PE-binding protein 1 (PEBP1). However, the mechanism of NO● interference with 15LOX/PEBP1 activity remained unclear. Here, we use a biochemical model of recombinant 15LOX-2 complexed with PEBP1, LC-MS redox lipidomics, and structure-based modeling and simulations to uncover the mechanism through which NO● suppresses ETE-PE oxidation. Our study reveals that O2 and NO● use the same entry pores and channels connecting to 15LOX-2 catalytic site, resulting in a competition for the catalytic site. We identified residues that direct O2 and NO● to the catalytic site, as well as those stabilizing the esterified ETE-PE phospholipid tail. The functional significance of these residues is supported by in silico saturation mutagenesis. We detected nitrosylated PE species in a biochemical system consisting of 15LOX-2/PEBP1 and NO● donor and in RAW264.7 M2 macrophages treated with ferroptosis-inducer RSL3 in the presence of NO●, in further support of the ability of NO● to diffuse to, and react at, the 15LOX-2 catalytic site. The results provide first insights into the molecular mechanism of repression of the ferroptotic Hp-ETE-PE production by NO●.

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“…Such conformations can be created computationally by taking advantage of biophysical methods such as molecular dynamics simulations (MD) (Adcock & McCammon, 2006) and normal mode analysis (NMA) (Bahar et al, 2010), simulating the movements defining a transition between two conformations. In this case, we used a trajectory from a recent study (Zhang et al, 2021b), which was generated using a purely NMA-based approach called the adaptive anisotropic network model (adaptive ANM; Yang et al, 2010) implemented in ProDy (Zhang et al, 2021a). This gave us 30 different models along an open-closed transition of the mammalian chaperonin CCT complex between two atomic models derived from a previous cryo-EM study (Cong et al, 2012), taken from the Protein Data Bank (PDB) (wwPDB Consortium, 2019), as described by Zhang et al (2021b).…”

Section: Experiments 2: Trajectory Recovery Of the Cct Complexmentioning

confidence: 99%

Approximating deformation fields for the analysis of continuous heterogeneity of biological macromolecules by 3D Zernike polynomials

Herreros

Lederman

Krieger

et al. 2021

Int Union Crystallogr J

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Structural biology has evolved greatly due to the advances introduced in fields like electron microscopy. This image-capturing technique, combined with improved algorithms and current data processing software, allows the recovery of different conformational states of a macromolecule, opening new possibilities for the study of its flexibility and dynamic events. However, the ensemble analysis of these different conformations, and in particular their placement into a common variable space in which the differences and similarities can be easily recognized, is not an easy matter. To simplify the analysis of continuous heterogeneity data, this work proposes a new automatic algorithm that relies on a mathematical basis defined over the sphere to estimate the deformation fields describing conformational transitions among different structures. Thanks to the approximation of these deformation fields, it is possible to describe the forces acting on the molecules due to the presence of different motions. It is also possible to represent and compare several structures in a low-dimensional mapping, which summarizes the structural characteristics of different states. All these analyses are integrated into a common framework, providing the user with the ability to combine them seamlessly. In addition, this new approach is a significant step forward compared with principal component analysis and normal mode analysis of cryo-electron microscopy maps, avoiding the need to select components or modes and producing localized analysis.

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ProDy 2.0: increased scale and scope after 10 years of protein dynamics modelling with Python

Cited by 114 publications

References 19 publications

ClustENMD: efficient sampling of biomolecular conformational space at atomic resolution

ClustENMD: efficient sampling of biomolecular conformational space at atomic resolution

NO● Represses the Oxygenation of Arachidonoyl PE by 15LOX/PEBP1: Mechanism and Role in Ferroptosis

Approximating deformation fields for the analysis of continuous heterogeneity of biological macromolecules by 3D Zernike polynomials

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