title: Prediction of cyclohexane-water distribution coefficient for SAMPL5 drug-like compounds with the QMPFF3 and ARROW polarizable force fields.
abstract: We present the performance of blind predictions of water-cyclohexane distribution coefficients for 53 drug-like compounds in the SAMPL5 challenge by three methods currently in use within our group. Two of them utilize QMPFF3 and ARROW, polarizable force-fields of varying complexity, and the third uses the General Amber Force-Field (GAFF). The polarizable FF's are implemented in an in-house MD package, Arbalest. We find that when we had time to parametrize the functional groups with care (batch 0), the polarizable force-fields outperformed the non-polarizable one. Conversely, on the full set of 53 compounds, GAFF performed better than both QMPFF3 and ARROW. We also describe the torsion-restrain method we used to improve sampling of molecular conformational space and thus the overall accuracy of prediction. The SAMPL5 challenge highlighted several drawbacks of our force-fields, such as our significant systematic over-estimation of hydrophobic interactions, specifically for alkanes and aromatic rings.
authors: InterX Inc., 811 Carleton Street, Berkeley, CA, 94710, USA.
authors: Ganesh
authors: G
authors: Kamath
authors: InterX Inc., 811 Carleton Street, Berkeley, CA, 94710, USA.
authors: Igor
authors: I
authors: Kurnikov
authors: InterX Inc., 811 Carleton Street, Berkeley, CA, 94710, USA.
authors: Boris
authors: B
authors: Fain
authors: InterX Inc., 811 Carleton Street, Berkeley, CA, 94710, USA.
authors: Igor
authors: I
authors: Leontyev
authors: InterX Inc., 811 Carleton Street, Berkeley, CA, 94710, USA.
authors: Alexey
authors: A
authors: Illarionov
authors: InterX Inc., 811 Carleton Street, Berkeley, CA, 94710, USA.
authors: Oleg
authors: O
authors: Butin
authors: InterX Inc., 811 Carleton Street, Berkeley, CA, 94710, USA.
authors: Michael
authors: M
authors: Olevanov
authors: InterX Inc., 811 Carleton Street, Berkeley, CA, 94710, USA. leonid.pereyaslavets@interxinc.com.
authors: Leonid
authors: 0000-0001-5410-2318
authors: L
authors: Pereyaslavets
mesh_terms: D003198:Computer Simulation; D003510:Cyclohexanes / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D003510:Cyclohexanes; D004364:Pharmaceutical Preparations; D054852:Small Molecule Libraries; D012997:Solvents; D014867:Water; C506365:Cyclohexane
keywords: ARROW; Free energies; GAFF; Polarizable force fields; QMPFF3; SAMPL5