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FEARCF a multidimensional free energy method for investigating conformational landscapes and chemical reaction mechanisms

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Abstract

The development and implementation of a computational method able to produce free energies in multiple dimensions, descriptively named the free energies from adaptive reaction coordinate forces (FEARCF) method is described in this paper. While the method can be used to calculate free energies of association, conformation and reactivity here it is shown in the context of chemical reaction landscapes. A reaction free energy surface for the Claisen rearrangement of chorismate to prephenate is used as an illustration of the method’s efficient convergence. FEARCF simulations are shown to achieve flat histograms for complex multidimensional free energy volumes. The sampling efficiency by which it produces multidimensional free energies is demonstrated on the complex puckering of a pyranose ring, that is described by a three dimensional W(θ 1, θ 2, θ 3) potential of mean force.

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Authors and Affiliations

  1. Scientific Computing Research Unit and Department of Chemistry, University of Cape Town, Cape Town, South Africa, 7701

    Kevin J. Naidoo

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  1. Kevin J. Naidoo
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Correspondence to Kevin J. Naidoo.

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NAIDOO Kevin J. holds a PhD from the University of Michigan (USA) and following this he was a Postdoctoral Fellow (1994–1995) at Cornell University (USA). He is Professor in Physical Chemistry at the University of Cape Town (UCT). Since 2007 he has held the South African Research Chair in Scientific Computing. He is the recipient of national honours, such as the title of Extraordinary Professor in the faculty of Natural Sciences given to him by University of the Western Cape (2010). Internationally he has served as member of the editorial board of the Journal of Computational Chemistry since 2004. In 2009 he established the Scientific Computing Research Unit (SCRU) at UCT. Luminaries such as Dr. Neil Lane, the Science advisor to the President of the United States Bill Clinton, have visited his laboratory.

His research group develops computational methods for investigating chemical and reactions and catalytic processes. In 2009 Nvidia Corporation awarded Prof. Naidoo an Nvidia Professor Partnership grant to advance the group’s research programme that is centered, on the development of quantum code that is accelerated by Graphical Processing Units (GPUs). This compliments is the highly successful sampling FEARCF (Free Energies from Reaction Coordinate Forces) method that has been developed over the last 12 years. The key goal is to produce hybrid ab initio-classical mechanics (QM/MM) software capable of nanosecond simulations on GPU based clusters.

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Naidoo, K.J. FEARCF a multidimensional free energy method for investigating conformational landscapes and chemical reaction mechanisms. Sci. China Chem. 54, 1962–1973 (2011). https://doi.org/10.1007/s11426-011-4423-7

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