In Silico Designing of an Industrially Sustainable Carbonic Anhydrase Using Molecular Dynamics Simulation

Bharatiy, Sachin Kumar; Hazra, Mousumi; Paul, Manish; Mohapatra, Swati; Samantaray, Deviprasad; Dubey, Ramesh Chandra; Sanyal, Shourjya; Datta, Saurav; Hazra, Saugata

doi:10.1021/acsomega.6b00041

Cited by 43 publications

(24 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inter‐molecular polar interactions are essential for maintaining the stable conformation of protein heterodimer and the orientation between 2 monomers, respectively . To assess the stability of heterodimer complex upon the binding of ligands, the hydrogen bonds (H‐bonds) and salt bridges between 2 monomers were analyzed.…”

Section: Resultsmentioning

confidence: 99%

Molecular dynamics investigation of stereoselective inhibition mechanism of HIF‐2α/ARNT heterodimer

Sun

Zheng

Zhang

2017

J of Molecular Recognition

View full text Add to dashboard Cite

Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors related with the onset and progression of solid tumors. Studies demonstrated a class of tetrazole containing chiral inhibitors could stereoselectively disrupt the HIF-2 dimerization and reduce the target gene expression. However, the dynamical features and structural motifs of the HIF-2 heterodimer caused by the binding of enantiomers have not been rationalized at the atomistic level. In this work, molecular dynamics (MD) simulations combined with adaptive steered MD (ASMD) simulations were used to investigate stereoselective interrupting mechanism of HIF-2. Our results decipher that the binding of ligand A (S, R)-24 begets the significant conformation changes of β-sheets and interrupts the HIF-2α/ARNT heterodimerization, which may be attributed to the disruption of the hydrogen bond and salt bridge interactions formed by the 4 foremost residues (Asp240, Arg247, Glu362, and Arg366) and the destruction of hydrophobic interactions on the binding interface. By contrast, the binding of ligand B (R, S)-24 does not disrupt protein dimerization and causes the motion of Fα helix in HIF-2α PAS-B domain to further change the major tunnel for ligand ingress and engress. The present work provides important molecular-level insight into the effect of the binding enantiomers on HIF-2 heterodimerization and bridges the gap between theory and the experimental results, which may conduce to develop highly potent antagonists for intervening the HIF-2-driven tumors.

show abstract

Section: Resultsmentioning

confidence: 99%

Molecular dynamics investigation of stereoselective inhibition mechanism of HIF‐2α/ARNT heterodimer

Sun

Zheng

Zhang

2017

J of Molecular Recognition

View full text Add to dashboard Cite

show abstract

“…We have used this parser in our lab for analyzing numerous macromolecular structures, virtual screening and docking results, non-covalent interaction studies, .pdb files from molecular dynamics simulations and other structure based data-set studies. In a case study (see supplementary material), we are able to identify stabilizing and destabilizing salt bridges from two homologous mesophilic and thermophilic α-carbonic anhydrase [17]. Studying these types of structural factors like salt bridges, surface residues, and active site water molecules for any macromolecular system is much more simple, fast and errorfree.…”

Section: Extension For Biochemical Applicationsmentioning

confidence: 99%

Parsers, Data Structures and Algorithms for Macromolecular Analysis Toolkit (MAT): Design and Implementation

Kalyan

Junghare

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

The structural information of biological macromolecules are stored in .pdb, .mmcif and lately mmtf files and thus it requires accurate and efficient biological tools for various utilities. Here, we describe Macromolecular Analysis Toolkit (MAT) that parses .pdb, .mmcif and .mmtf files; and builds data structures from the input. This original program is written in C++ programming language to ensure efficiency and consistency to organize structural information in an integral way. The novelty of the program lies in the addition of new structure-based biological algorithms and applications. This package also stands out from other similar libraries by being 1) faster and 2) accurate. We also provide detailed comparison of available parsers on the whole PDB database. The parser of MAT is designed in such a way that it allows quick extraction and organized loading of the core data structure. The same data structure is extended to accommodate information from the .mmcif and .mmtf file parsers. Tokenization of the data allows the extraction of information from disordered text, making it compatible for accurate identification of the entities present in the .pdb file. Additionally, we add a new approach of performance optimization by creating a few derived data structures, namely kD-Tree, Octree and graphs, for certain applications that need spatial coordinate calculations. MAT provides advanced data structure which is time efficient and is designed to avail reusability and consistency in * Corresponding a systematic framework. MAT parser can be accessed online through bitbucket at https://bitbucket.org/gazalk/pdb_parser/.

show abstract

“…() and Bharatiy et al . () used a combined approach of rational enzyme engineering and molecular dynamics to obtain halotolerant CA and industrially suitable thermostable CA (~225°C), respectively. Alvizo et al .…”

Section: Summary and Future Perspectivementioning

confidence: 99%

“…The use of molecular dynamics, rational engineering, directed evolution and the use of multimeric enzymes is found to be very limited by scientists in finding potential CA for CCUS. Warden et al (2015) and Bharatiy et al (2016) used a combined approach of rational enzyme engineering and molecular dynamics to obtain halotolerant CA and industrially suitable thermostable CA (~225°C), respectively. Alvizo et al (2014) developed ultra-thermostable (107°C) CA using directed evolution.…”

Section: Other Lesser Pondered Areamentioning

confidence: 99%

Trends, application and future prospectives of microbial carbonic anhydrase mediated carbonation process for CCUS

2017

View full text Add to dashboard Cite

Summary Growing industrialization and the desire for a better economy in countries has accelerated the emission of greenhouse gases (GHGs), by more than the buffering capacity of the earth's atmosphere. Among the various GHGs, carbon dioxide occupies the first position in the anthroposphere and has detrimental effects on the ecosystem. For decarbonization, several non‐biological methods of carbon capture, utilization and storage (CCUS) have been in use for the past few decades, but they are suffering from narrow applicability. Recently, CO2 emission and its disposal related problems have encouraged the implementation of bioprocessing to achieve a zero waste economy for a sustainable environment. Microbial carbonic anhydrase (CA) catalyses reversible CO2 hydration and forms metal carbonates that mimic the natural phenomenon of weathering/carbonation and is gaining merit for CCUS. Thus, the diversity and specificity of CAs from different micro‐organisms could be explored for CCUS. In the literature, more than 50 different microbial CAs have been explored for mineral carbonation. Further, microbial CAs can be engineered for the mineral carbonation process to develop new technology. CA driven carbonation is encouraging due to its large storage capacity and favourable chemistry, allowing site‐specific sequestration and reusable product formation for other industries. Moreover, carbonation based CCUS holds five‐fold more sequestration capacity over the next 100 years. Thus, it is an eco‐friendly, feasible, viable option and believed to be the impending technology for CCUS. Here, we attempt to examine the distribution of various types of microbial CAs with their potential applications and future direction for carbon capture. Although there are few key challenges in bio‐based technology, they need to be addressed in order to commercialize the technology.

show abstract

In Silico Designing of an Industrially Sustainable Carbonic Anhydrase Using Molecular Dynamics Simulation

Cited by 43 publications

References 62 publications

Molecular dynamics investigation of stereoselective inhibition mechanism of HIF‐2α/ARNT heterodimer

Molecular dynamics investigation of stereoselective inhibition mechanism of HIF‐2α/ARNT heterodimer

Parsers, Data Structures and Algorithms for Macromolecular Analysis Toolkit (MAT): Design and Implementation

Trends, application and future prospectives of microbial carbonic anhydrase mediated carbonation process for CCUS

Contact Info

Product

Resources

About