GMXPBSA 2.1: A GROMACS tool to perform MM/PBSA and computational alanine scanning

Paissoni, Cristina; Spiliotopoulos, Dimitrios; Musco, Giovanna; Spitaleri, Andrea

doi:10.1016/j.cpc.2014.09.010

Cited by 81 publications

(61 citation statements)

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“…17,18 Compared with DNA-graphene-based materials, the interactions between protein and a graphene surface have not been fully studied. 18 In this work, we focused on the interaction of lysozyme and a graphene sheet using MD simulations in combination with the molecular mechanics/ Poisson-Boltzmann surface area (MM/PBSA) method 19,20 to compute the protein-surface binding free energy by postprocessing MD trajectory with implicit water medium. The graphene surface is characterized by an ordered flat chemical structure, lacking of dangling bonds or roughness, yields zero atomistic charge, and homogenous hydrophobicity and chemistry.…”

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confidence: 99%

Study of lysozyme mobility and binding free energy during adsorption on a graphene surface

Nakano

Wei

2015

Applied Physics Letters

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Understanding protein adsorption is a key to the development of biosensors and anti-biofouling materials. Hydration essentially controls the adsorption process on hydrophobic surfaces, but its effect is complicated by various factors. Here, we present an ideal model system to isolate hydration effects—lysozyme adsorption on a flat hydrophobic graphene surface. Our all-atom molecular dynamics and molecular-mechanics/Poisson-Boltzmann surface area computation study reveal that lysozyme on graphene displays much larger diffusivity than in bulk water. Protein's hydration free energy within the first hydration shell is dominated by the protein-water electrostatic interactions and acts as an energy barrier for protein adsorption. On the other hand, the surface tension, especially that from the hydrophobic graphene, can effectively weaken the barrier to promote adsorption.

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confidence: 99%

Study of lysozyme mobility and binding free energy during adsorption on a graphene surface

Nakano

Wei

2015

Applied Physics Letters

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“…To evaluate the binding strength of selected ligands with protein, we carried out binding free energy calculation using the molecular dynamics‐based GMXPBSA method that is widely used to calculate bimolecular interaction/binding energies using the PBSA method. The binding free energy of protein–ligand complex was calculated as follows:

Δ G_{normalbinding} = G_{normalcomplex} - false(G_{protein} + G_{ligand} false)

…”

Section: Methodsmentioning

confidence: 99%

Identification of natural inhibitors of Bcr‐Abl for the treatment of chronic myeloid leukemia

et al. 2017

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Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of the hematopoietic stem cells, characterized at the molecular level by the bcr/abl gene rearrangement. Even though targeting the fusion gene product Bcr-Abl protein is a successful strategy, development of drug resistance and that of drug intolerance are currently the limitations for Bcr-Abl-targeted CML therapy. With an aim to develop natural Bcr-Abl inhibitors, we performed virtual screening (VS) of ZINC natural compound database by docking with Abl kinase using Glide software. Two natural inhibitors ZINC08764498 (hit1) and ZINC12891610 (hit2) were selected by considering their high Glide docking score and critical interaction with the hinge region residue Met-318 of Abl kinase. The reactivity of the two molecules was assessed computationally by density functional theory calculations. Further, the conformational transition, hydrogen bond interactions, and the binding energies were investigated during 10-ns molecular dynamics simulation of the Abl-hit complex. When tested in vitro, hit1 compared to hit2 showed selective inhibition of cell proliferation and induction of apoptosis in Bcr-Abl-positive K-562 leukemia cells. In summary, our results demonstrate that ZINC08764498, a coumarin derivative identified through VS, is a potential natural inhibitor for the treatment of CML.

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“…The protein and solvent were modeled with dielectric constants of ε =2 and ε =80, respectively. APBS suite [35] and GMXPBSA [36] were used for implicit solvent calculations. In this study, we attempted to calculate the entropic estimate of binding using the interaction entropy formalism [37].…”

Section: Protein Structure Modelingmentioning

confidence: 99%

Predicting and Designing therapeutics against the Nipah virus

Sen¹,

Kanitkar²,

Roy³

et al. 2019

Preprint

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Though every outbreak of the Nipah Virus has resulted in high mortality rates (>70% in Southeast Asia), there are no licensed drugs against it. In this study we have considered all 9 Nipah proteins as potential therapeutic targets and computationally identified putative peptides (against G, F, and M proteins) and small molecules inhibitors (against F, G, M, N, and P proteins). The computations include extensive homology/ab initio modelling, peptide design and small molecule docking. An important contribution of this study is the increased structural characterization of Nipah proteins by approximately 90% of what is deposited in the PDB. In addition, we have carried out molecular dynamics simulations on all the designed proteinpeptide complexes to check for stability and to estimate binding strengths. Details, including atomic coordinates of all the proteins and their ligand bound complexes, can be accessed at http://cospi.iiserpune.ac.in/Nipah. Our strategy was to tackle the development of therapeutics on a proteome wide scale and the lead compounds identified could be attractive starting points for drug development. To this end, we have designed 4 peptide inhibitors and predicted 70 small molecules (13 with high confidence) against 3 and 5 Nipah proteins respectively. To counter the threat of drug resistance, we have analyzed the sequences of the viral strains from different outbreaks, to check whether they would be sensitive to the binding of the proposed inhibitors.

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GMXPBSA 2.1: A GROMACS tool to perform MM/PBSA and computational alanine scanning

Cited by 81 publications

References 0 publications

Study of lysozyme mobility and binding free energy during adsorption on a graphene surface

Study of lysozyme mobility and binding free energy during adsorption on a graphene surface

Identification of natural inhibitors of Bcr‐Abl for the treatment of chronic myeloid leukemia

Predicting and Designing therapeutics against the Nipah virus

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