Accuracy of free energies of hydration using CM1 and CM3 atomic charges

Udier-Blagovi, Marina; Tirado, Patricia Morales De; Pearlman, Shoshannah A.; Jorgensen, William L.

doi:10.1002/jcc.20059

Cited by 142 publications

(229 citation statements)

References 44 publications

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“…This probably happens because of the united atom descriptions of the two methyl groups with zero partial charges, rather than because of the problems modeling the charge distributions of the peptide groups. The dipole moment of the NMA model with off-center charges (4.38 D) has been purposefully kept almost unchanged when compared with the original GROMOS 53A6 values (4.14 D), similar to the reported experimental values of 4.39 D. 54 Solvation free energies of NMA have been reported using other biomolecular force field, some underestimation when compared with experimental results have also been reported except for CHARMM (232.87 kJ mol 21 for OPLS, 59 247.26 kJ mol 21 for CHARMM, 60 and 237.2 kJ mol 21 for AMBER 61 ). All these studies have employed all-atom models and significant amount of partial charges have been assigned on atoms of the methyl groups.…”

Section: The Off-center Charge Modelsupporting

confidence: 60%

Refining the description of peptide backbone conformations improves protein simulations using the GROMOS 53A6 force field

Cao¹,

Lin²,

Wang³

2008

J Comput Chem

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The GROMOS 53A6 parameter sets have been shown to reproduce an extensive range of thermodynamics data in condensed phase (Oostenbrink et al., J Comput Chem 2004, 25, 1656), mainly due to the reoptimized nonbonded interactions. Here, we derive refinements for the descriptions of peptide backbone conformations for this parameter set. A two-dimensional adaptive umbrella sampling procedure was employed to determine the free energy surfaces of model alanine and glycine dipeptides in solution to high accuracy, with sampling errors below 0.8 kJ mol(-1) for relative free energies between major minima. Comparisons of these surfaces with quantum mechanical ones and conformation distributions in protein crystal structures indicated that refined treatments of backbone torsional angle terms are necessary. The high accuracy of the computed free energy surfaces allowed us to consider two types of corrections, one numerically and exactly reproducing the quantum mechanical results, and the other using small analytical terms to correct major deficiencies for the dipeptide systems. In addition, aiming at improving the directionality of backbone-backbone hydrogen bonds, we optimized and tested an off-center charge model for the peptide backbone carbonyl oxygen. Extensive molecular dynamics simulations of five proteins and two peptides in solution indicate that refined treatments of backbone dihedral angles lead to substantial improvements of the simulations. Being much simpler, the analytical terms perform as good as or even slightly better than the exact numerical corrections. Although using off-center charges brought some improvements, the directionality of hydrogen bonds have not been significantly improved.

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Section: The Off-center Charge Modelsupporting

confidence: 60%

Refining the description of peptide backbone conformations improves protein simulations using the GROMOS 53A6 force field

Cao¹,

Lin²,

Wang³

2008

J Comput Chem

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“…1. It can be expected that improvements will be made in the future to reduce the average errors to Ͻ0.5 kcal͞mol (34,56,57).…”

Section: Free Energies Of Hydrationmentioning

confidence: 99%

“…Although there are many other issues with force-field development (6, 7), generalization to the treatment of any organic molecule is a particular challenge (15,(56)(57)(58). The advent of combinatorial chemistry and the variety of heterocycles that are used in medicinal chemistry stress the need.…”

Section: Universal Force Fieldsmentioning

confidence: 99%

“…Their rapid procedures, which yield highly accurate dipole moments, are incorporated directly into our software for computing charges for arbitrary organic molecules for both force-field and QM͞MM calculations (62,63). The different CM alternatives have been tested in computations of free energies of hydration in TIP4P water by using OPLS-AA parameters except for the charges (56). The best results come from the AM1-based CM1A charges scaled by 1.14 for neutral molecules.…”

Section: Universal Force Fieldsmentioning

confidence: 99%

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Potential energy functions for atomic-level simulations of water and organic and biomolecular systems

Jorgensen

Tirado‐Rives

2005

Proc. Natl. Acad. Sci. U.S.A.

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1,203

1,021

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An overview is provided on the development and status of potential energy functions that are used in atomic-level statistical mechanics and molecular dynamics simulations of water and of organic and biomolecular systems. Some topics that are considered are the form of force fields, their parameterization and performance, simulations of organic liquids, computation of free energies of hydration, universal extension for organic molecules, and choice of atomic charges. The discussion of water models covers some history, performance issues, and special topics such as nuclear quantum effects.T he last 30 years have witnessed remarkable progress in condensed-phase theory. Before that time, atomic-level computer simulations of fluids were largely restricted to atomic and diatomic systems. The first simulation of liquid water was not reported until 1969 and was a Monte Carlo (MC) effort (1), which was followed by the molecular dynamics (MD) studies of Rahman and Stillinger (2, 3) in the early 1970s. The state-of-the-art simulations of water in 1974 were performed for 216 molecules for Ͻ10 ps (3). Even by 1990, there had been almost no MD simulations for a protein in aqueous solution covering 100 ps (4), whereas today MD simulations for a protein with Ϸ10,000 water molecules for many nanoseconds or mixed quantum and molecular mechanics (QM͞ MM) simulations for an enzymatic reaction are not problematic. Of course, performing longer simulations for larger systems does not guarantee the production of useful results. Key underlying issues for accuracy are adequate configurational sampling and the quality of the description of the intramolecular and intermolecular energetics. Progress on the former issue has been aided greatly by massive increases in computing power, although the substantial technical developments in the latter area are the focus of this overview. The topic also has received attention in comprehensive, recent reviews for the treatment of water (5) and biomolecular systems (6-10) that go far beyond the present page limitations. So, the presentation here will be more condensed with a focus on force-field development, water, and aqueous solutions and with some emphasis on our personal experiences and viewpoint. Force FieldsA force field consists of classical potential energy expressions and the associated adjustable parameters. The large majority of condensed-phase simulations have invoked pairwise additivity such that the total potential energy for a collection of molecules and͞or ions (components) with coordinates X ជ is given by the sum of the intermolecular interaction energies between all components plus the sum of the intramolecular energies of the components (Eq. 1).The intramolecular potential energy is typically represented by harmonic terms for bond stretching and angle bending, a Fourier series for each torsional angle, and Coulomb and Lennard-Jones interactions between atoms separated by three or more bonds (Eqs. 2-5). The latter ''nonbonded'' interactions also are evaluated between intermolecular at...

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“…Molecular dynamics (MD) calculations were performed according to the classical all atom optimized potential for liquid simulations (OPLS-AA) 30 for the inter-and intrachain interactions using the simulation (SIM) package. 31 The interactions of the atoms of the chains with the graphite lattice are described by a Lennard-Jones potential 32 in combination with an image charge interaction term.…”

mentioning

confidence: 99%

Scanning Tunneling Microscopy Images of Alkane Derivatives on Graphite: Role of Electronic Effects

et al. 2008

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Scanning tunneling microscopy (STM) images of self-assembled monolayers of close-packed alkane chains on highly oriented pyrolitic graphite often display an alternating bright and dark spot pattern. Classical simulations suggest that a tilt of the alkane backbone is unstable and, therefore, unlikely to account for the contrast variation. First principles calculations based on density functional theory show that an electronic effect can explain the observed alternation. Furthermore, the asymmetric spot pattern associated with the minimum energy alignment is modulated depending on the registry of the alkane adsorbate relative to the graphite surface, explaining the characteristic moiré pattern that is often observed in STM images with close packed alkyl assemblies.

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Accuracy of free energies of hydration using CM1 and CM3 atomic charges

Cited by 142 publications

References 44 publications

Refining the description of peptide backbone conformations improves protein simulations using the GROMOS 53A6 force field

Refining the description of peptide backbone conformations improves protein simulations using the GROMOS 53A6 force field

Potential energy functions for atomic-level simulations of water and organic and biomolecular systems

Scanning Tunneling Microscopy Images of Alkane Derivatives on Graphite: Role of Electronic Effects

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