The effect of numerical error on the reproducibility of molecular geometry optimizations
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| Udgivet i: | Journal of Computer - Aided Molecular Design vol. 22, no. 1 (Jan 2008), p. 39 |
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Springer Nature B.V.
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| Online adgang: | Citation/Abstract Full Text Full Text - PDF |
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| Resumen: | Geometry optimization is one of the most often applied techniques in computational drug discovery. Although geometry optimization routines are generally deterministic, the minimization trajectories can be extremely sensitive to initial conditions, especially in case of larger systems such as proteins. Simple manipulations such as coordinate transformations (translations and rotations), file saving and retrieving, and hydrogen addition can introduce small variations (0.001 Å) in the starting coordinates which can drastically affect the minimization trajectory. With large systems, optimized geometry differences of up to 1 Å RMSD and final energy differences of several kcal/mol can be observed when using many commercially available software packages. Differences in computer platforms can also lead to differences in minimization trajectories. Here we demonstrate how routine structure manipulations can introduce small variations in atomic coordinates, which upon geometry optimization, can give rise to unexpectedly large differences in optimized geometries and final energies. We also show how the same minimizations run on different computer platforms can also lead to different results. The implications of these findings on routine computational chemistry procedures are discussed. [PUBLICATION ABSTRACT] Geometry optimization is one of the most often applied techniques in computational drug discovery. Although geometry optimization routines are generally deterministic, the minimization trajectories can be extremely sensitive to initial conditions, especially in case of larger systems such as proteins. Simple manipulations such as coordinate transformations (translations and rotations), file saving and retrieving, and hydrogen addition can introduce small variations ( approximately 0.001 A) in the starting coordinates which can drastically affect the minimization trajectory. With large systems, optimized geometry differences of up to 1 A RMSD and final energy differences of several kcal/mol can be observed when using many commercially available software packages. Differences in computer platforms can also lead to differences in minimization trajectories. Here we demonstrate how routine structure manipulations can introduce small variations in atomic coordinates, which upon geometry optimization, can give rise to unexpectedly large differences in optimized geometries and final energies. We also show how the same minimizations run on different computer platforms can also lead to different results. The implications of these findings on routine computational chemistry procedures are discussed. |
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| ISSN: | 0920-654X 1573-4951 |
| DOI: | 10.1007/s10822-007-9154-7 |
| Fuente: | Science Database |