An integrative approach using systems biology, mutational analysis with molecular dynamics simulation to challenge the functionality of a target protein

Bora, Nikita; Jha, Anupam Nath

doi:10.1111/cbdd.13502

Cited by 24 publications

(10 citation statements)

References 58 publications

(73 reference statements)

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“…To comprehend the functionality and dynamics of the protein and protein–ligand systems, MDS has been extensively utilized. − Therefore, in order to understand the dynamic behavior of the protein in the presence of NPs, molecular dynamics simulations were carried out with the GROMACS (Groningen Machine for Chemical Simulations) 2016.4 version. , The parameterized GROMOS 54A7 force field was utilized for all of the simulations. In this study, seven sets of simulations were carried out, that is, that of only the HSA protein and of the AgNP and five sets of protein–NP conjugate systems.…”

Section: Methodsmentioning

confidence: 99%

Computational Analysis of the Silver Nanoparticle–Human Serum Albumin Complex

Hazarika

Jha

2019

ACS Omega

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Drug delivery in excess concentrations and at not-specified sites inside the human body adversely affects the body and gives rise to other diseases. Several methods have been developed to deliver the drugs in required amounts and at specific targets. Nanoparticle-mediated drug delivery is one such approach and has gained success at primary levels. The effect of nanoparticles on the human body needs important apprehension, and it has been unraveled by assessing the protein–nanoparticle interactions. Here, we have measured the impact of silver nanoparticles (AgNPs) on the human serum albumin (HSA) structure and function with the help of all-atom molecular dynamics simulations (MDS). HSA is a transport protein, and any change in the structure may obstruct its function. The post MD analyses showed that the NP interacts with HSA and the conjugated system got stabilized with time evolution of trajectories. The present investigation confirms that the AgNP interacts with HSA without affecting its tertiary and secondary structures and in turn the protein function as well. AgNP application is recommended in transporting conjugated drug molecules as it has no adverse effect on serum proteins. Since HSA is present in the circulatory system, it may open various applications of AgNPs in the biomedical field.

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Section: Methodsmentioning

confidence: 99%

Computational Analysis of the Silver Nanoparticle–Human Serum Albumin Complex

Hazarika

Jha

2019

ACS Omega

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“…Systems biology is interdisciplinary and includes a wide range of data from in vivo, in vitro, in situ, and in silico studies. Ideally, in silico studies would be integrated and validated by other data sources especially when applicable outcomes are aimed (Butcher et al, 2004;Dunn et al, 2010;Bora and Jha, 2019).…”

Section: Systems Biology: Concepts and Applicationsmentioning

confidence: 99%

Perspectives From Systems Biology to Improve Knowledge of Leishmania Drug Resistance

Horácio

Hickson

Murta

et al. 2021

Front. Cell. Infect. Microbiol.

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Neglected Tropical Diseases include a broad range of pathogens, hosts, and vectors, which represent evolving complex systems. Leishmaniasis, caused by different Leishmania species and transmitted to humans by sandflies, are among such diseases. Leishmania and other Trypanosomatidae display some peculiar features, which make them a complex system to study. Leishmaniasis chemotherapy is limited due to high toxicity of available drugs, long-term treatment protocols, and occurrence of drug resistant parasite strains. Systems biology studies the interactions and behavior of complex biological processes and may improve knowledge of Leishmania drug resistance. System-level studies to understand Leishmania biology have been challenging mainly because of its unusual molecular features. Networks integrating the biochemical and biological pathways involved in drug resistance have been reported in literature. Antioxidant defense enzymes have been identified as potential drug targets against leishmaniasis. These and other biomarkers might be studied from the perspective of systems biology and systems parasitology opening new frontiers for drug development and treatment of leishmaniasis and other diseases. Our main goals include: 1) Summarize current advances in Leishmania research focused on chemotherapy and drug resistance. 2) Share our viewpoint on the application of systems biology to Leishmania studies. 3) Provide insights and directions for future investigation.

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“…With the advancement of both experimental and computational techniques, availability of 3D data in regard to proteins, proteins complexes, membrane proteins etc. has been possible which made the system size amplified to several lakhs of atoms with explicit solvent in consideration [50]. Meanwhile the advent of high-performance computing (HPC) and algorithm parallelization made it possible to run long timescale simulations for the above-mentioned systems.…”

Section: Molecular Dynamics: the Computational Microscopementioning

confidence: 99%

Role of Force Fields in Protein Function Prediction

Hazarika¹,

Rajkhowa²,

Jha³

2021

Homology Molecular Modeling - Perspectives and Applications

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The world today, although, has developed an elaborate health system to fortify against known and unknown diseases, it continues to be challenged by new as well as emerging, and re-emerging infectious disease threats with severity and probable fluctuations. These threats also have varying costs for morbidity and mortality, as well as for a complex set of socioeconomic outcomes. Some of these diseases are often caused by pathogens which use humans as host. In such cases, it becomes paramount responsibility to dig out the source of pathogen survival to stop their population growth. Sequencing genomes has been finessed so much in the 21st century that complete genomes of any pathogen can be sequenced in a matter of days following which; different potential drug targets are needed to be identified. Structure modeling of the selected sequences is an initial step in structure-based drug design (SBDD). Dynamical study of predicted models provides a stable target structure. Results of these in-silico techniques greatly depend on force field (FF) parameters used. Thus, in this chapter, we intend to discuss the role of FF parameters used in protein structure prediction and molecular dynamics simulation to provide a brief overview on this area.

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An integrative approach using systems biology, mutational analysis with molecular dynamics simulation to challenge the functionality of a target protein

Cited by 24 publications

References 58 publications

Computational Analysis of the Silver Nanoparticle–Human Serum Albumin Complex

Computational Analysis of the Silver Nanoparticle–Human Serum Albumin Complex

Perspectives From Systems Biology to Improve Knowledge of Leishmania Drug Resistance

Role of Force Fields in Protein Function Prediction

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