The influence of polarization functions on molecular orbital hydrogenation energies

Hariharan, P. C.; Pople, John A.

doi:10.1007/bf00533485

Cited by 14,778 publications

(8,717 citation statements)

References 16 publications

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“…For Trp 35 Phe/Trp 71 Tyr, inclusion of the explicit residues gives small shifts, with the largest shift, to the red, calculated for the 1 L a transition energy in the calculation where most residues are treated explicitly by TDDFT (R ) 5.0 Å). Addition of the extended environment via point charges red-shifts all the transitions, with the 1 L a transition energy for R ) 5.0 Å having the greatest red shift.…”

Section: Resultsmentioning

confidence: 99%

“…However, in addition to point charges, we include neighboring residues explicitly, which are required to observe shifts in the transition energies that are predicted to be different for each of the mutants at the TDDFT level of theory. For the Trp 35 Phe/Trp 94 Phe mutant with the extended point charge environment, transitions to the two excited states of interest proved difficult to assign, due to a large degree of configurational mixing. A generic disadvantage of TDDFT is that for a particular excited state no permanent expectation values, such as dipole moments and wave function spatial extents, may be obtained, which would otherwise aid in the assignment of the excited state.…”

Section: Resultsmentioning

confidence: 99%

“…AMBER snapshot geometries in the absence of long-range interactions combined with AMBER point charges were a good (and time saving) approximation. These methods were selected based on the bathochromic shifts of the two lowest transitions of indole and on the relative energy difference of the states in the environment of the Trp 35 Phe/Trp 94 Phe mutant.…”

Section: Introductionmentioning

confidence: 99%

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Modeling the Absorption Spectrum of Tryptophan in Proteins

et al. 2005

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We have applied time-dependent density functional theory (TDDFT) to study the valence π-π* excited states of the tryptophan chromophore in the environment of the proteins barnase and human serum albumin. The chromophore is represented by indole. Due to the approximate nature of TDDFT, in the gas phase the calculated vertical transition energies to the 1 L valence states are reordered with respect to experiment. The 1 L a state responds more than the 1 L b state to the local environment, described fully at the TDDFT level, and to bulk environment, described by a set of point charges. Nevertheless, the vertical transitions are readily identified. For human serum albumin, our calculations predict distinct spectral characteristics between structures with different tryptophan side chain torsion angles. The computational tractability of TDDFT relative to more accurate ab initio methods allows a large part of the surrounding protein environment (up to 100 atoms) to be explicitly included in the TDDFT calculations.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modeling the Absorption Spectrum of Tryptophan in Proteins

et al. 2005

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“…The 6-31(þ)G* basis set 33 was used throughout, that is the diffuse functions were added only to the negatively charged carboxylic groups (where those were present). The core orbitals (1s of C, O, and N) were not correlated in the MP2 calculations.…”

Section: Calculation Detailsmentioning

confidence: 99%

Pair interaction energy decomposition analysis

2006

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Abstract:The energy decomposition analysis (EDA) by Kitaura and Morokuma was redeveloped in the framework of the fragment molecular orbital method (FMO). The proposed pair interaction energy decomposition analysis (PIEDA) can treat large molecular clusters and the systems in which fragments are connected by covalent bonds, such as proteins. The interaction energy in PIEDA is divided into the same contributions as in EDA: the electrostatic, exchange-repulsion, and charge transfer energies, to which the correlation (dispersion) term was added. The careful comparison to the ab initio EDA interaction energies for water clusters with 2-16 molecules revealed that PIEDA has the error of at most 1.2 kcal/mol (or about 1%). The analysis was applied to (H 2 O) 1024 , the helix, turn, and strand of polyalanine (ALA) 10 , as well as to the synthetic protein (PDB code 1L2Y) with 20 residues. The comparative aspects of the polypeptide isomer stability are discussed in detail.

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“…66 The optimized conformers of flapup and flap-down oxocarbenium ions were determined by constraining the dihedral angle made by C-2, C-1, O-5 and C-5 to 0° and allowing all other parameters to optimize at BLYP/6-31G* level of theory. The hydroxyl groups of the resulting structures were placed in three different orientations representing three rotamers and the conformers were reoptimized without any restraints at B3LYP/6-31G* level.…”

Section: Geometry Optimization Of Flap-up and Flap-down Conformers Ofmentioning

confidence: 99%

Structural Basis of the Inhibition of Golgi α-Mannosidase II by Mannostatin A and the Role of the Thiomethyl Moiety in Ligand−Protein Interactions

et al. 2006

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The X-ray crystal structures of mannose trimming enzyme Drosophila Golgi α-mannosidase II (dGMII) complexed with the inhibitors mannostatin A (1) and an N-benzyl analog (2) have been determined. Molecular dynamics simulations and NMR studies have shown that the five-membered ring of mannostatin A is rather flexible occupying pseudo-rotational itineraries between 2 T 3 and 5 E, and 2 T 3 and 4 E. In the bound state, mannostatin A adopts a 2 T 1 twist envelope conformation, which is not significantly populated in solution. Possible conformations of the mannosyl oxacarbenium ion and an enzyme-linked intermediate have been compared to the conformation of mannostatin A in the co-crystal structure with dGMII. It has been found that mannostatin A best mimics the covalent linked mannosyl intermediate, which adopts a 1 S 5 skew boat conformation. The thiomethyl group, which is critical for high affinity, superimposes with the C-6 hydroxyl of the covalent linked intermediate. This functionality is able to make a number of additional polar and non-polar interactions increasing the affinity for dGMII. Furthermore, the X-ray structures show that the environment surrounding the thiomethyl group of 1 is remarkably similar to the arrangements around the methionine residues in the protein. Collectively, our studies contradict the long held view that potent inhibitors of glycosidases mimic an oxacarbenium ion like transition state.

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The influence of polarization functions on molecular orbital hydrogenation energies

Cited by 14,778 publications

References 16 publications

Modeling the Absorption Spectrum of Tryptophan in Proteins

Modeling the Absorption Spectrum of Tryptophan in Proteins

Pair interaction energy decomposition analysis

Structural Basis of the Inhibition of Golgi α-Mannosidase II by Mannostatin A and the Role of the Thiomethyl Moiety in Ligand−Protein Interactions

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