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SAMPL6 host-guest challenge: binding free energies via a multistep approach.
Eken, Yigitcan; Patel, Prajay; Díaz, Thomas; Jones, Michael R; Wilson, Angela K.
Afiliación
  • Eken Y; Department of Chemistry, Michigan State University, East Lansing, MI, 48824, USA.
  • Patel P; Department of Chemistry, Michigan State University, East Lansing, MI, 48824, USA.
  • Díaz T; Department of Chemistry, Michigan State University, East Lansing, MI, 48824, USA.
  • Jones MR; Department of Chemistry, Michigan State University, East Lansing, MI, 48824, USA.
  • Wilson AK; Department of Chemistry, Michigan State University, East Lansing, MI, 48824, USA. akwilson@msu.edu.
J Comput Aided Mol Des ; 32(10): 1097-1115, 2018 10.
Article en En | MEDLINE | ID: mdl-30225724
In this effort in the SAMPL6 host-guest binding challenge, a combination of molecular dynamics and quantum mechanical methods were used to blindly predict the host-guest binding free energies of a series of cucurbit[8]uril (CB8), octa-acid (OA), and tetramethyl octa-acid (TEMOA) hosts bound to various guest molecules in aqueous solution. Poses for host-guest systems were generated via molecular dynamics (MD) simulations and clustering analyses. The binding free energies for the structures obtained via cluster analyses of MD trajectories were calculated using the MMPBSA method and density functional theory (DFT) with the inclusion of Grimme's dispersion correction, an implicit solvation model to model the aqueous solution, and the resolution-of-the-identity (RI) approximation (MMPBSA, RI-B3PW91-D3, and RI-B3PW91, respectively). Among these three methods tested, the results for OA and TEMOA systems showed MMPBSA and RI-B3PW91-D3 methods can be used to qualitatively rank binding energies of small molecules with an overbinding by 7 and 37 kcal/mol respectively, and RI-B3PW91 gave the poorest quality results, indicating the importance of dispersion correction for the binding free energy calculations. Due to the complexity of the CB8 systems, all of the methods tested show poor correlation with the experimental results. Other quantum mechanical approaches used for the calculation of binding free energies included DFT without the RI approximation, utilizing truncated basis sets to reduce the computational cost (memory, disk space, CPU time), and a corrected dielectric constant to account for ionic strength within the implicit solvation model.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hidrocarburos Aromáticos con Puentes / Ácidos Carboxílicos / Proteínas / Cicloparafinas / Compuestos Macrocíclicos / Imidazoles Tipo de estudio: Prognostic_studies Idioma: En Revista: J Comput Aided Mol Des Asunto de la revista: BIOLOGIA MOLECULAR / ENGENHARIA BIOMEDICA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hidrocarburos Aromáticos con Puentes / Ácidos Carboxílicos / Proteínas / Cicloparafinas / Compuestos Macrocíclicos / Imidazoles Tipo de estudio: Prognostic_studies Idioma: En Revista: J Comput Aided Mol Des Asunto de la revista: BIOLOGIA MOLECULAR / ENGENHARIA BIOMEDICA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos