Accuracy assessment of semiempirical molecular electrostatic potential of proteins

Anisimov, Victor M.; Anikin, N. A.; Bugaenko, V. L.; Bobrikov, Vladimir V.; Andreyev, Alexey

doi:10.1007/s00214-002-0400-8

Cited by 5 publications

(6 citation statements)

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“…19 Many other articles have appeared in the literature using semiempirical methods for the calculation of systems important for biochemistry: calculation of pKa of proteins, 20 -22 studies of enzymatic reaction mechanisms 23-26 calculation of spectroscopic properties of proteins, 31 among many others. [32][33][34][35][36][37][38] A recent study showed a molecular dynamics calculation of the protein crambin, in solution, where the protein was treated with a semiempirical method and the solvent by a molecular mechanics force field. Results reproduced much more accurately aspects of the geometry of the protein than would be obtained by a pure force field approach.…”

Section: Introductionmentioning

confidence: 99%

RM1: A reparameterization of AM1 for H, C, N, O, P, S, F, Cl, Br, and I

Rocha¹,

Freire²,

Simas³

et al. 2006

J Comput Chem

670

435

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Twenty years ago, the landmark AM1 was introduced, and has since had an increasingly wide following among chemists due to its consistently good results and time-tested reliability--being presently available in countless computational quantum chemistry programs. However, semiempirical molecular orbital models still are of limited accuracy and need to be improved if the full potential of new linear scaling techniques, such as MOZYME and LocalSCF, is to be realized. Accordingly, in this article we present RM1 (Recife Model 1): a reparameterization of AM1. As before, the properties used in the parameterization procedure were: heats of formation, dipole moments, ionization potentials and geometric variables (bond lengths and angles). Considering that the vast majority of molecules of importance to life can be assembled by using only six elements: C, H, N, O, P, and S, and that by adding the halogens we can now build most molecules of importance to pharmaceutical research, our training set consisted of 1736 molecules, representative of organic and biochemistry, containing C, H, N, O, P, S, F, Cl, Br, and I atoms. Unlike AM1, and similar to PM3, all RM1 parameters have been optimized. For enthalpies of formation, dipole moments, ionization potentials, and interatomic distances, the average errors in RM1, for the 1736 molecules, are less than those for AM1, PM3, and PM5. Indeed, the average errors in kcal x mol(-1) of the enthalpies of formation for AM1, PM3, and PM5 are 11.15, 7.98, and 6.03, whereas for RM1 this value is 5.77. The errors, in Debye, of the dipole moments for AM1, PM3, PM5, and RM1 are, respectively, 0.37, 0.38, 0.50, and 0.34. Likewise, the respective errors for the ionization potentials, in eV, are 0.60, 0.55, 0.48, and 0.45, and the respective errors, in angstroms, for the interatomic distances are 0.036, 0.029, 0.037, and 0.027. The RM1 average error in bond angles of 6.82 degrees is only slightly higher than the AM1 figure of 5.88 degrees, and both are much smaller than the PM3 and PM5 figures of 6.98 degrees and 9.83 degrees, respectively. Moreover, a known error in PM3 nitrogen charges is corrected in RM1. Therefore, RM1 represents an improvement over AM1 and its similar successor PM3, and is probably very competitive with PM5, which is a somewhat different model, and not fully disclosed. RM1 possesses the same analytical construct and the same number of parameters for each atom as AM1, and, therefore, can be easily implemented in any software that already has AM1, not requiring any change in any line of code, with the sole exception of the values of the parameters themselves.

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Section: Introductionmentioning

confidence: 99%

RM1: A reparameterization of AM1 for H, C, N, O, P, S, F, Cl, Br, and I

Rocha¹,

Freire²,

Simas³

et al. 2006

J Comput Chem

670

435

View full text Add to dashboard Cite

show abstract

“…Here, the least errors are observed for the MNDO Hamiltonian, followed by AM1, then PM3, and at last, PM5. Because the AM1 Hamiltonian is considered to be of primary interest among other semiempirical Hamiltonians for biological applications, − it is especially important that our results confirm that AM1 does not introduce any particular complications for the linear scaling regimen. Regarding the PM5 Hamiltonian, both LocalSCF and MOZYME results indicate that PM5 makes more difficult in comparison to other Hamiltonians the task of achieving the linear scaling regimen.…”

Section: Resultsmentioning

confidence: 64%

“…In our analysis, the dipole moment differences are calculated in the vector form using eq 2. This approach is shown to be more sensitive to the errors in calculations of the dipole moment . Because proteins have large dipole moments, even a 1% error in orientation of the dipole vector may have serious implications.…”

Section: Resultsmentioning

confidence: 99%

“…This approach is shown to be more sensitive to the errors in calculations of the dipole moment. 22 Because proteins have large dipole moments, even a 1% error in orientation of the dipole vector may have serious implications. Because insulin has a charge of +1, the center of mass was taken as the origin for the dipole moment calculation.…”

Section: Regular Mode Calculation Of Small Proteinmentioning

confidence: 99%

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Validation of Linear Scaling Semiempirical LocalSCF Method

Anisimov

Bugaenko

Bobrikov

2006

J. Chem. Theory Comput.

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The numerical accuracy of linear scaling semiempirical methods LocalSCF and MOZYME is analyzed in comparison to conventional matrix diagonalization with respect to a variety of molecular properties including conformational energy, dipole moment, atomic charges, and bond orders. Major semiempirical MNDO, AM1, PM3, and PM5 Hamiltonians were considered in the study. As the numerical tests demonstrate, both LocalSCF and MOZYME reasonably reproduce matrix diagonalization results with the deviations being below the accuracy of semiempirical methods. However, the economical LocalSCF memory consumption and faster calculations are more beneficial for the quantum-mechanical modeling of large biological systems. The computational performance of the LocalSCF method is tested on the conformational energy calculation of a series of molecular dynamics snapshots of insulin in a large box of water.

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“…Semiempirical methods have been used widely over the last decades in studies ranging from geometry optimizations and molecular modeling to reproduction of physical data such as heat of formation, proton affinity, spectroscopic parameters, and reaction energies. − Semiempirical methods are popular because of their relatively modest time and computational costs compared with QM methods and their relative ease of applicability for study of reactive processes at active sites compared with MM force field methods. − Semiempirical methods have also been studied in detail; for example, the accuracies of semiempirical electrostatic potentials and potential-derived charges − and the appropriateness of these methods in treating QM/MM interactions , have been evaluated. However, to our knowledge, no studies have yet been reported that assess the performance of semiempirical methods in describing noncovalent halogen bonding.…”

Section: Introductionmentioning

confidence: 99%

Performance Assessment of Semiempirical Molecular Orbital Methods in Describing Halogen Bonding: Quantum Mechanical and Quantum Mechanical/Molecular Mechanical-Molecular Dynamics Study

Ibrahim

2011

J. Chem. Inf. Model.

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The performance of semiempirical molecular-orbital methods--MNDO, MNDO-d, AM1, RM1, PM3 and PM6--in describing halogen bonding was evaluated, and the results were compared with molecular mechanical (MM) and quantum mechanical (QM) data. Three types of performance were assessed: (1) geometrical optimizations and binding energy calculations for 27 halogen-containing molecules complexed with various Lewis bases (Two of the tested methods, AM1 and RM1, gave results that agree with the QM data.); (2) charge distribution calculations for halobenzene molecules, determined by calculating the solvation free energies of the molecules relative to benzene in explicit and implicit generalized Born (GB) solvents (None of the methods gave results that agree with the experimental data.); and (3) appropriateness of the semiempirical methods in the hybrid quantum-mechanical/molecular-mechanical (QM/MM) scheme, investigated by studying the molecular inhibition of CK2 protein by eight halobenzimidazole and -benzotriazole derivatives using hybrid QM/MM molecular-dynamics (MD) simulations with the inhibitor described at the QM level by the AM1 method and the rest of the system described at the MM level. The pure MM approach with inclusion of an extra point of positive charge on the halogen atom approach gave better results than the hybrid QM/MM approach involving the AM1 method. Also, in comparison with the pure MM-GBSA (generalized Born surface area) binding energies and experimental data, the calculated QM/MM-GBSA binding energies of the inhibitors were improved by replacing the G(GB,QM/MM) solvation term with the corresponding G(GB,MM) term.

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Accuracy assessment of semiempirical molecular electrostatic potential of proteins

Cited by 5 publications

References 0 publications

RM1: A reparameterization of AM1 for H, C, N, O, P, S, F, Cl, Br, and I

RM1: A reparameterization of AM1 for H, C, N, O, P, S, F, Cl, Br, and I

Validation of Linear Scaling Semiempirical LocalSCF Method

Performance Assessment of Semiempirical Molecular Orbital Methods in Describing Halogen Bonding: Quantum Mechanical and Quantum Mechanical/Molecular Mechanical-Molecular Dynamics Study

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