Protocol for MM/PBSA Molecular Dynamics Simulations of Proteins

Fogolari, Federico; Brigo, Alessandro; Molinari, Henríette

doi:10.1016/s0006-3495(03)74462-2

Cited by 174 publications

(126 citation statements)

References 55 publications

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“…First of all, one may run MD simulations using implicit water models, such as in GBSA and PBSA, instead of an explicit water model. PB-MD [112] and GB-MD have been available in Macromodel [113] and the AMBER software packages. Although the conformations sampled by PB-MD and GB-MD for post energetic analysis may not be as good as those sampled by MD in explicit solvent, PB-MD and GB-MD can save a lot of CPU hours not only in the sampling stage, but also in the post-analysis stage since many solvation energy terms are calculated during the simulations.…”

Section: Perspective and Conclusionmentioning

confidence: 99%

Recent Advances in Free Energy Calculations with a Combination of Molecular Mechanics and Continuum Models

Wang¹,

Hou²,

2006

CAD

332

262

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Abstract:Recently, the combination of state-of-the-art molecular mechanical force fields with continuum solvation models enables us to make relatively accurate predictions of both structures and free energies for macromolecules from molecular dynamics trajectories. The first part of this review is focused on the history and basic theory of free energy calculations based on physically effective energy functions. The second part illustrates the applications of free energy calculations on many biological systems, including proteins, DNA, RNA, protein-ligand, protein-protein, protein-nucleic acid complexes, etc. Finally, the prospective and possible strategies to improve the techniques of MM-PBSA and MM-GBSA is discussed.

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Section: Perspective and Conclusionmentioning

confidence: 99%

Recent Advances in Free Energy Calculations with a Combination of Molecular Mechanics and Continuum Models

Wang¹,

Hou²,

2006

CAD

332

262

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“…An attempt to calculate the T⌬S contribution using a harmonic approximation yielded essentially the same results for 100 snapshots of the three complexes with large standard deviations (Ϸ19 Ϯ 13 kcal/mol), mostly because of the vibrational contribution of the systems. A quasi-harmonics approach could be used to calculate entropy, but the 10-ns trajectories are normally not sufficient to reach a convergence of entropic values (49). The T⌬S contribution was therefore not included in the analysis, an approximation classically used when comparing binding of different ligands and/or different mutants (50,51).…”

Section: Acceptormentioning

confidence: 99%

Role of Water Molecules in Structure and Energetics of Pseudomonas aeruginosa Lectin I Interacting with Disaccharides

Nurisso

Blanchard

Audfray

et al. 2010

Journal of Biological Chemistry

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Calcium-dependent lectin I from Pseudomonas aeruginosa (PA-IL) binds specifically to oligosaccharides presenting an ␣-galactose residue at their nonreducing end, such as the disaccharides ␣Gal1-2␤GalOMe, ␣Gal1-3␤GalOMe, and ␣Gal1-4␤GalOMe. This provides a unique model for studying the effect of the glycosidic linkage of the ligands on structure and thermodynamics of the complexes by means of experimental and theoretical tools. The structural features of PA-IL in complex with the three disaccharides were established by docking and molecular dynamics simulations and compared with those observed in available crystal structures, including PA-IL⅐␣Gal1-2␤GalOMe complex, which was solved at 2.4 Å resolution and reported herein. The role of a structural bridge water molecule in the binding site of PA-IL was also elucidated through molecular dynamics simulations and free energy calculations. This water molecule establishes three very stable hydrogen bonds with O6 of nonreducing galactose, oxygen from Pro-51 main chain, and nitrogen from Gln-53 main chain of the lectin binding site. Binding free energies for PA-IL in complex with the three disaccharides were investigated, and the results were compared with the experimental data determined by titration microcalorimetry. When the bridge water molecule was included in the free energy calculations, the simulations predicted the correct binding affinity trends with the 1-2-linked disaccharide presenting three times stronger affinity ligand than the other two. These results highlight the role of the water molecule in the binding site of PA-IL and indicate that it should be taken into account when designing glycoderivatives active against P. aeruginosa adhesion.

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“…Although the PB equation may be solved numerically and can be applied to heterogeneous environments, [16][17][18][19][20] it is generally difficult to balance efficiency and accuracy in direct solutions to the PB equation for the purpose of molecular dynamics simulations. [21][22][23][24] The generalized Born (GB) model offers an efficient analytical approximation to the electrostatic solvation free energy of a solute in aqueous solution according to PB theory. 25 A number of GB variants have been proposed in recent years that are summarized in a recent review.…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics Simulations of Large Integral Membrane Proteins with an Implicit Membrane Model

Tanizaki

Feig

2005

J. Phys. Chem. B

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The heterogeneous dielectric generalized Born (HDGB) methodology is an the extension of the GBMV model for the simulation of integral membrane proteins with an implicit membrane environment. Three large integral membrane proteins, the bacteriorhodopsin monomer and trimer and the BtuCD protein, were simulated with the HDGB model in order to evaluate how well thermodynamic and dynamic properties are reproduced. Effects of the truncation of electrostatic interactions were examined. For all proteins, the HDGB model was able to generate stable trajectories that remained close to the starting experimental structures, in excellent agreement with explicit membrane simulations. Dynamic properties evaluated through a comparison of B-factors are also in good agreement with experiment and explicit membrane simulations. However, overall flexibility was slightly underestimated with the HDGB model unless a very large electrostatic cutoff is employed. Results with the HDGB model are further compared with equivalent simulations in implicit aqueous solvent, demonstrating that the membrane environment leads to more realistic simulations.

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Protocol for MM/PBSA Molecular Dynamics Simulations of Proteins

Cited by 174 publications

References 55 publications

Recent Advances in Free Energy Calculations with a Combination of Molecular Mechanics and Continuum Models

Recent Advances in Free Energy Calculations with a Combination of Molecular Mechanics and Continuum Models

Role of Water Molecules in Structure and Energetics of Pseudomonas aeruginosa Lectin I Interacting with Disaccharides

Molecular Dynamics Simulations of Large Integral Membrane Proteins with an Implicit Membrane Model

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