Reassociation of fragments using multicentered multipolar expansions: peptide junction treatments to investigate electrostatic properties of proteins

Dardenne, Laurent E.; Werneck, Araken S.; Neto, Mario Oliveira; Bisch, Paulo Mascarello

doi:10.1002/jcc.1037

Cited by 11 publications

(16 citation statements)

References 35 publications

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“…In this first library, the multipolar expansions centered in the terminal atom or terminal bond are redistributed to make the number and the localization of the final expansion centers to be the same as if the whole protein had not been subdivided in small fragments (for details see Ref. 46). …”

Section: Protein Fragmentation Scheme and The Ome Methods Of Reassociamentioning

confidence: 99%

“…The direct PM contribution is computed using the OME reassociation method of fragments 46 based in multicentered multipolar expansions 59 -61 derived directly from ab initio quantum wave functions obtained from calculations on overlapping fragments (i.e., amino acids) of the protein.…”

Section: Electrostatic Calculationsmentioning

confidence: 99%

“…30,[63][64][65] Moreover, previous studies indicate that in protein electrostatic investigations the OME reassociation method is the best choice in order to achieve a better and more homogeneous description of both the electrostatic potential and the intensity and direction of the electric field. 46 The RF contribution is calculated using the continuum electrostatic approximation. In this approximation, the protein/solvent system is divided in two distinct regions separated by a two-dimensional surface ⌺ enclosing the protein matrix charge distribution and the charge distribution of the explicit active site water molecules.…”

Section: Electrostatic Calculationsmentioning

confidence: 99%

“…68 The fragment input files to the GAMESS program are generated automatically manner by a program written by us, using as input the atomic coordinates of the refined protein structure in a PDB file format. The first library is used by another program 46 that performs all the steps of the OME procedure necessary to generate the final library of fragment multicentered multipolar expansions. This final library is used by an adapted version of the SIBFA program 69 to calculate the electrostatic potential and the electric field PM contribution in a set of predefined points.…”

Section: Electrostatics In the Papain Catalytic Sitementioning

confidence: 99%

“…45 In this article, we investigated the electrostatic profile in the Cys25/His159 catalytic region of papain, aiming to identify its characteristics and the possible enzymatic regulatory mechanisms in the region where the catalytic residues interact with the ligand and with the active site water molecules. We used a recently developed methodology, the OME (overlapping of multipolar expansions) reassociation method, 46 to obtain a more precise description of the electrostatic field due to the protein matrix charge distribution. To include solvent effects, in the continuum electrostatic approximation, the OME reassociation method is coupled to two distinct boundary valued methods in order to solve the Poisson 47,48 and the linearized Poisson-Boltzmann 49 -51 equations.…”

Section: Introductionmentioning

confidence: 99%

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Electrostatic properties in the catalytic site of papain: A possible regulatory mechanism for the reactivity of the ion pair

et al. 2003

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We present an analysis of the electrostatic properties in the catalytic site of papain (EC 3.4.22.2), an archetype enzyme of the C1 cysteine proteinase family, and we investigate their possible role in the formation, stabilization and regulation of the Cys25 (؊) …His159 (؉) catalytic ion pair. The electrostatic properties were computed using a reassociation method based in multicentered multipolar expansions obtained from ab initio quantum calculations of overlapping protein fragments. Solvent effects were introduced by coupling the use of multicentered multipolar expansions to two continuum boundary element methods to solve the Poisson and the linearized Poisson-Boltzmann equations. The electrostatic profile found in the proton transfer region of papain showed that this enzyme has a well-defined electrostatic environment to favor the formation and stabilization of the catalytic ion pair. The papain catalytic site electrostatic profile can be considered as an electrostatic fingerprint of the papain family with the following characteristics: (i) the presence of a net electric field highly aligned in the (Cys25)-SG3(His159)-ND1 direction; (ii) the electrostatic profile has a saddlepoint character; (iii) it is basically a local environmental effect. Furthermore, our analysis describes a possible regulatory mechanism (the E SG3 ND1 attenuation effect) controlling the ion pair reactivity and permits to infer the Asp57 acidic residue as the most probable candidate to act as the electrostatic modulator. Proteins 2003;52:236 -253.

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Section: Protein Fragmentation Scheme and The Ome Methods Of Reassociamentioning

confidence: 99%

Section: Electrostatic Calculationsmentioning

confidence: 99%

Section: Electrostatic Calculationsmentioning

confidence: 99%

Section: Electrostatics In the Papain Catalytic Sitementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Electrostatic properties in the catalytic site of papain: A possible regulatory mechanism for the reactivity of the ion pair

et al. 2003

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Intraprotein electrostatics derived from first principles: Divide‐and‐conquer approaches for QM/MM calculations

Molina

Jensen

2003

J Comput Chem

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Two divide-and-conquer (DAQ) approaches for building multipole-based molecular electrostatic potentials of proteins are presented and evaluated for use in QM/MM calculations. One approach is a further development of the neutralization method of Bellido and Rullmann (J Comput Chem 1989, 10, 479-487) while the other is based on removing part of the electron density before performing the multipole expansion. Both methods create systems with integer charges without using charge renormalization. To determine their performance in terms of location of cuts and distance to QM region, the new DAQ approaches are tested in calculations of the proton affinity of N(zeta) of Lys55 in the inhibitor turkey ovomucoid third domain. Finally, the two methods are used to build a variety of MM regions, applied to calculations of the pK(a) of Lys55, and compared to other computational methodologies in which force field charges are employed.

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Intramolecular interaction energies in model alanine and glycine tetrapeptides. Evaluation of anisotropy, polarization, and correlation effects. A parallel ab initio HF/MP2, DFT, and polarizable molecular mechanics study

Gresh

Kafafi²,

Truchon

et al. 2004

J Comput Chem

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An extension of the SIBFA polarizable molecular mechanics procedure to flexible oligopeptides is reported. The procedure is evaluated by computing the relative conformational energies, deltaE(conf), of the alanine tetrapeptide in 10 representative conformations, which were originally derived by Beachy et al. (J Am Chem Soc 1997, 119, 5908) to benchmark molecular mechanics procedures with respect to ab initio computations. In the present study, a particular emphasis is on the separable nature of the components of the energy and the particular impact of the polarization energy component on deltaE(conf). We perform comparisons with respect to single-point HF, DFT, LMP2, and MP2 computations done at the SIBFA-derived energy minima. Such comparisons are made first for the 10 conformers derived from phi/psi torsional angle energy-minimization (the rigid rotor approach), and, in a second step, after allowing additional relaxation of the C(alpha) centered valence angles. In both series of energy-minimization, the SIBFA deltaE(conf) compared best with the LMP2 results using the 6-311G** basis set, the rms being 1.3 kcal/mol. In the absence of the polarization component, the rms is 3.5 kcal/mol. In both series of minimizations, the magnitudes of deltaE(conf), computed as differences with respect to the most stable conformer taken as energy zero, decrease along the series: HF > DFT > LMP2 > SIBFA > MP2, indicative of increasing stabilization of the most highly folded conformers.

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Reassociation of fragments using multicentered multipolar expansions: peptide junction treatments to investigate electrostatic properties of proteins

Cited by 11 publications

References 35 publications

Electrostatic properties in the catalytic site of papain: A possible regulatory mechanism for the reactivity of the ion pair

Electrostatic properties in the catalytic site of papain: A possible regulatory mechanism for the reactivity of the ion pair

Intraprotein electrostatics derived from first principles: Divide‐and‐conquer approaches for QM/MM calculations

Intramolecular interaction energies in model alanine and glycine tetrapeptides. Evaluation of anisotropy, polarization, and correlation effects. A parallel ab initio HF/MP2, DFT, and polarizable molecular mechanics study

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