Papers by Izaz Monir Kamal
Journal of biomolecular structure and dynamics/Journal of biomolecular structure & dynamics, Feb 12, 2024
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Journal of Biomolecular Structure & Dynamics, Jan 19, 2022
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Journal of Cellular Biochemistry, Mar 31, 2023
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ACS omega, Jan 31, 2023
Molecular docking plays a major role in academic and industrial drug screening and discovery proc... more Molecular docking plays a major role in academic and industrial drug screening and discovery processes. Despite the availability of numerous docking software packages, there is a lot of scope for improvement for the docking algorithms in terms of becoming more reliable to replicate the experimental binding results. Here, we propose a combinatorial or consensus docking approach where complementary powers of the existing methods are captured. We created a meta-docking protocol by combining the results of AutoDock4.2, LeDock, and rDOCK programs as these are freely available, easy to use, and suitable for large-scale analysis and produced better performance on benchmarking studies. Rigorous benchmarking analyses were undertaken to evaluate the scoring, posing, and screening capability of our approach. Further, the performance measures were compared against one standard state-of-the-art commercial docking software, GOLD, and one freely available software, PLANTS. Performances of MetaDOCK for scoring, posing, and screening the protein−ligand complexes were found to be quite superior compared to the reference programs. Exhaustive molecular dynamics simulation and molecular mechanics Poisson−Boltzmann and surface area-based free energy estimation also suggest better energetic stability of the docking solutions produced by our meta-approach. We believe that the MetaDOCK approach is a useful packaging of the freely available software and provides a better alternative to the scientific community who are unable to afford costly commercial packages.
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Journal of Biomolecular Structure and Dynamics
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ACS Omega, 2023
Molecular docking plays a major role in academic and industrial drug screening and
discovery pro... more Molecular docking plays a major role in academic and industrial drug screening and
discovery processes. Despite the availability of numerous docking software packages, there is a lot of scope for improvement for the docking algorithms in terms of becoming more reliable to replicate the experimental binding results. Here, we propose a combinatorial or consensus docking approach where complementary powers of the existing methods are captured. We created a meta-docking protocol by combining the results of AutoDock4.2, LeDock, and rDOCK programs as these are freely available,
easy to use, and suitable for large-scale analysis and produced better performance on benchmarking studies. Rigorous benchmarking analyses were undertaken to evaluate the scoring, posing, and screening capability of our approach. Further, the performance measures were compared against one standard state-of-the-art commercial docking software, GOLD, and one freely available software, PLANTS. Performances of MetaDOCK for scoring, posing, and screening the protein−ligand complexes were found to be quite superior compared to the reference programs. Exhaustive molecular
dynamics simulation and molecular mechanics Poisson−Boltzmann and surface area-based free energy estimation also suggest better energetic stability of the docking solutions produced by our meta-approach. We believe that the MetaDOCK approach is a useful packaging of the freely available software and provides a better alternative to the scientific community who are unable to afford costly commercial packages.
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Journal of Biomolecular Structure and Dynamics, 2022
SARS-CoV-2, a new coronavirus emerged in 2019, causing a global healthcare epidemic. Although a v... more SARS-CoV-2, a new coronavirus emerged in 2019, causing a global healthcare epidemic. Although a variety of drug targets have been identified as potential antiviral therapies, and effective candidate against SARS-CoV-2 remains elusive. One of the most promising targets for combating COVID-19 is SARS-CoV-2 Main protease (Mpro, a protein responsible for viral replication. In this work, an in-house curated library was thoroughly evaluated for druggability against Mpro. We identified four ligands (FG, Q5, P5, and PJ4) as potential inhibitors based on docking scores, predicted binding energies (MMGBSA), in silico ADME, and RMSD trajectory analysis. Among the selected ligands, FG, a natural product from Andrographis nallamalayana, exhibited the highest binding energy of -10.31 kcal/mol close to the docking score of clinical candidates Boceprevir and GC376. Other ligands (P5, natural product from cardiospermum halicacabum and two synthetic molecules Q5 and PJ4) have shown comparable docking scores ranging -7.65 kcal/mol to -7.18 kcal/mol. Interestingly, we found all four top ligands had Pi bond interaction with the main amino acid residues HIS41 and CYS145 (catalytic dyad), H-bonding interactions with GLU166, ARG188, and GLN189, and hydrophobic interactions with MET49 and MET165 in the binding site of Mpro. According to the ADME analysis, Q5 and P5 are within the acceptable range of drug likeliness, compared to FG and PJ4. The interaction stability of the lead molecules with viral protease was verified using replicated MD simulations. Thus, the present study opens up the opportunity of developing drug candidates targeting SARS-CoV-2 main protease (Mpro) to mitigate the disease.
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Frontiers in Genetics, 2021
The novel coronavirus 2 (nCoV2) outbreaks took place in December 2019 in Wuhan City, Hubei Provin... more The novel coronavirus 2 (nCoV2) outbreaks took place in December 2019 in Wuhan City, Hubei Province, China. It continued to spread worldwide in an unprecedented manner, bringing the whole world to a lockdown and causing severe loss of life and economic stability. The coronavirus disease 2019 (COVID-19) pandemic has also affected India, infecting more than 10 million till 31st December 2020 and resulting in more than a hundred thousand deaths. In the absence of an effective vaccine, it is imperative to understand the phenotypic outcome of the genetic variants and subsequently the mode of action of its proteins with respect to human proteins and other bio-molecules. Availability of a large number of genomic and mutational data extracted from the nCoV2 virus infecting Indian patients in a public repository provided an opportunity to understand and analyze the specific variations of the virus in India and their impact in broader perspectives. Non-structural proteins (NSPs) of severe acu...
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Journal of Cell Science, 2021
Mutations in mitofusin 2 (MFN2) that are associated with the pathology of the debilitating neurop... more Mutations in mitofusin 2 (MFN2) that are associated with the pathology of the debilitating neuropathy Charcot–Marie–Tooth type 2A (CMT2A) are known to alter mitochondrial morphology. One such abundant MFN2 mutation, R364W, results in the generation of elongated, interconnected mitochondria. However, the mechanism leading to this mitochondrial aberration remains poorly understood. Here, we show that mitochondrial hyperfusion in the presence of R364W-MFN2 is due to increased degradation of DRP1 (also known as DNM1L). The E3 ubiquitin ligase MITOL (also known as MARCHF5) is known to ubiquitylate both MFN2 and DRP1. Interaction with and subsequent ubiquitylation by MITOL is stronger in the presence of wild-type MFN2 than with R364W-MFN2. This differential interaction of MITOL with MFN2 in the presence of R364W-MFN2 renders the ligase more available for DRP1 ubiquitylation. Multi-monoubiquitylation and proteasomal degradation of DRP1 in R364W-MFN2 cells in the presence of MITOL eventuall...
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Papers by Izaz Monir Kamal
discovery processes. Despite the availability of numerous docking software packages, there is a lot of scope for improvement for the docking algorithms in terms of becoming more reliable to replicate the experimental binding results. Here, we propose a combinatorial or consensus docking approach where complementary powers of the existing methods are captured. We created a meta-docking protocol by combining the results of AutoDock4.2, LeDock, and rDOCK programs as these are freely available,
easy to use, and suitable for large-scale analysis and produced better performance on benchmarking studies. Rigorous benchmarking analyses were undertaken to evaluate the scoring, posing, and screening capability of our approach. Further, the performance measures were compared against one standard state-of-the-art commercial docking software, GOLD, and one freely available software, PLANTS. Performances of MetaDOCK for scoring, posing, and screening the protein−ligand complexes were found to be quite superior compared to the reference programs. Exhaustive molecular
dynamics simulation and molecular mechanics Poisson−Boltzmann and surface area-based free energy estimation also suggest better energetic stability of the docking solutions produced by our meta-approach. We believe that the MetaDOCK approach is a useful packaging of the freely available software and provides a better alternative to the scientific community who are unable to afford costly commercial packages.
discovery processes. Despite the availability of numerous docking software packages, there is a lot of scope for improvement for the docking algorithms in terms of becoming more reliable to replicate the experimental binding results. Here, we propose a combinatorial or consensus docking approach where complementary powers of the existing methods are captured. We created a meta-docking protocol by combining the results of AutoDock4.2, LeDock, and rDOCK programs as these are freely available,
easy to use, and suitable for large-scale analysis and produced better performance on benchmarking studies. Rigorous benchmarking analyses were undertaken to evaluate the scoring, posing, and screening capability of our approach. Further, the performance measures were compared against one standard state-of-the-art commercial docking software, GOLD, and one freely available software, PLANTS. Performances of MetaDOCK for scoring, posing, and screening the protein−ligand complexes were found to be quite superior compared to the reference programs. Exhaustive molecular
dynamics simulation and molecular mechanics Poisson−Boltzmann and surface area-based free energy estimation also suggest better energetic stability of the docking solutions produced by our meta-approach. We believe that the MetaDOCK approach is a useful packaging of the freely available software and provides a better alternative to the scientific community who are unable to afford costly commercial packages.