Improving the performance of the MM/PBSA and MM/GBSA methods in recognizing the native structure of the Bcl-2 family using the interaction entropy method

Zhong, Susu; Huang, Kaifang; Luo, Song; Dong, Shuheng; Duan, Lili

doi:10.1039/c9cp06459a

Cited by 23 publications

(15 citation statements)

References 65 publications

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“…Furthermore, gmx_MMPBSA implements a new method for estimating the entropic term IE method, in addition to the two (NMODE and QH) already available in MMPBSA.py. The main advantage of this new method is its low computational cost, making it attractive for high throughput energy calculations. − Neither g_mmpbsa nor GMXPBSA2.1 has any of these methods implemented in their routines. Although several studies conclude that correlations based on effective energy may be sufficient, , others assert that entropic correction can improve these estimates. ,, In any case, we provide the user with different methods to estimate the entropic component that can be executed independently (Table ).…”

Section: Results and Discussionmentioning

confidence: 99%

gmx_MMPBSA: A New Tool to Perform End-State Free Energy Calculations with GROMACS

Valdés-Tresanco

Valdés‐Tresanco

Valiente

et al. 2021

J. Chem. Theory Comput.

1,242

468

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Molecular mechanics/Poisson–Boltzmann (Generalized-Born) surface area is one of the most popular methods to estimate binding free energies. This method has been proven to balance accuracy and computational efficiency, especially when dealing with large systems. As a result of its popularity, several programs have been developed for performing MM/PB(GB)SA calculations within the GROMACS community. These programs, however, present several limitations. Here we present gmx_MMPBSA, a new tool to perform end-state free energy calculations from GROMACS molecular dynamics trajectories. gmx_MMPBSA provides the user with several options, including binding free energy calculations with different solvation models (PB, GB, or 3D-RISM), stability calculations, computational alanine scanning, entropy corrections, and binding free energy decomposition. Noteworthy, several promising methodologies to calculate relative binding free energies such as alanine scanning with variable dielectric constant and interaction entropy have also been implemented in gmx_MMPBSA. Two additional toolsgmx_MMPBSA_test and gmx_MMPBSA_anahave been integrated within gmx_MMPBSA to improve its usability. Multiple illustrating examples can be accessed through gmx_MMPBSA_test, while gmx_MMPBSA_ana provides fast, easy, and efficient access to different graphics plotted from gmx_MMPBSA output files. The latest version (v1.4.3, 26/05/2021) is available free of charge (documentation, test files, and tutorials included) at .

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Section: Results and Discussionmentioning

confidence: 99%

gmx_MMPBSA: A New Tool to Perform End-State Free Energy Calculations with GROMACS

Valdés-Tresanco

Valdés‐Tresanco

Valiente

et al. 2021

J. Chem. Theory Comput.

1,242

468

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“…In order to evaluate the docking results of the three software servers, the top ranking pose from each was examined using the PDBePISA online tool, developed by The European Bioinformatics Institute, EMBL-EBI, for the exploration of macromolecular interfaces (Krissinel & Henrick, 2007 ). Moreover, a Molecular Mechanics energies combined with Generalized Born and Surface Area (MM/GBSA) calculation, as implemented within the Hawkdock server, was used to estimate the binding affinities (Hou et al., 2011 ; Zhong et al., 2020 ). The results of the examination of the top complex generated by each software are illustrated in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia

Helal

Shouman

Abdelwaly

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Lymphopenia is considered one of the most characteristic clinical features of the coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects host cells via the interaction of its spike protein with the human angiotensin-converting enzyme 2 (hACE2) receptor. Since T lymphocytes display a very low expression level of hACE2, a novel receptor might be involved in the entry of SARS-CoV-2 into T cells. The transmembrane glycoprotein CD147 is highly expressed by activated T lymphocytes, and was recently proposed as a probable route for SARS-CoV-2 invasion. To understand the molecular basis of the potential interaction of SARS-CoV-2 to CD147, we have investigated the binding of the viral spike protein to this receptor in-silico. The results showed that this binding is dominated by electrostatic interactions involving residues Arg403, Asn481, and the backbone of Gly502. The overall binding arrangement shows the CD147 C-terminal domain interacting with the spike external subdomain in the grove between the short antiparallel b strands, b1' and b2', and the small helix a1'. This proposed interaction was further confirmed using MD simulation and binding free energy calculation. These data contribute to a better understanding of the mechanism of infection of SARS-CoV-2 to T lymphocytes and could provide valuable insights for the rational design of adjuvant treatment for COVID-19.

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“…Molecular mechanics-generalized Born surface area (MM-GBSA) is a very popular method for estimating BFE , and widely used in the design of new drugs. , This method takes advantage of the fact that free energy is a function of thermodynamic state to create an alternative way to do the energy calculations as we see in Figure S6. In the MM-GBSA approach, the BFE of the receptor ligand (RL) complex, the receptor (R), and the ligand (L) are decomposed into several energy terms, as we see in the equations below where E mm is the molecular mechanic potential used in the force field, Δ G solv is the solvation energy and T Δ S is the entropic term.…”

Section: Methodsmentioning

confidence: 99%

“…MM-GBSA. Molecular mechanics-generalized Born surface area (MM-GBSA) is a very popular method for estimating BFE 45,58 and widely used in the design of new drugs. 47,59 This method takes advantage of the fact that free energy is a function of thermodynamic state to create an alternative way to do the energy calculations as we see in Figure S6.…”

Section: ■ Introductionmentioning

confidence: 99%

Genetic Algorithms Applied to Thermodynamic Rational Design of Mimetic Antibodies Based on the GB1 Domain of Streptococcal Protein G: An Atomistic Simulation Study

Santo

Feliciano

2021

J. Phys. Chem. B

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The development of mimetic antibodies (MA) capable of combining the high affinity and selectivity of antibodies with the small size of the peptides has enormous potential for applications in current biotechnology. In this work, we demonstrate that in silico MA design is possible through genetic algorithms (GA) developed from shell scripts capable of combining software commonly used for atomistic simulation. Our results demonstrate that, using the GB1 domain of the streptococcal G protein as a model, it is possible to optimize the molecular recognition capacity of a large MA population in a few generations. In the first case, GA was able to generate 10 MA with binding free energy (BFE) less than the vascular endothelial cell growth factor conjugated with the fms-type tyrosine kinase receptor. In the second case, it generated 13 MA with BFE less than that of the hepatitis C-E2 viral envelope conjugate with the antibody. Through the GA developed in this work, we demonstrate the use of a new protocol, capable of guiding experimental methods for the design of bioactive peptides that can assist in the development of new therapeutic molecules.

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Improving the performance of the MM/PBSA and MM/GBSA methods in recognizing the native structure of the Bcl-2 family using the interaction entropy method

Abstract: Correct discrimination of native structure plays an important role in drug design. IE method significantly improves the performance of MM/PB(GB)SA method in discriminating native and decoy structures in protein–ligand/protein systems of Bcl-2 family.

Cited by 23 publications

References 65 publications

gmx_MMPBSA: A New Tool to Perform End-State Free Energy Calculations with GROMACS

gmx_MMPBSA: A New Tool to Perform End-State Free Energy Calculations with GROMACS

Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia

Genetic Algorithms Applied to Thermodynamic Rational Design of Mimetic Antibodies Based on the GB1 Domain of Streptococcal Protein G: An Atomistic Simulation Study

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