TY - JOUR
T1 - Directional dependence of hydrogen bonds
T2 - A density-based energy decomposition analysis and its implications on force field development
AU - Lu, Zhenyu
AU - Zhou, Nengjie
AU - Wu, Qin
AU - Zhang, Yingkai
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/12/13
Y1 - 2011/12/13
N2 - One well-known shortcoming of widely used biomolecular force fields is the description of the directional dependence of hydrogen bonding (HB). Here we aim to better understand the origin of this difficulty and thus provide some guidance for further force field development. Our theoretical approaches center on a novel density-based energy decomposition analysis (DEDA) method (J. Chem. Phys. 2009, 131, 164112), in which the frozen density energy is variationally determined through constrained search. This unique and most significant feature of DEDA enables us to find that the frozen density interaction term is the key factor in determining the HB orientation, while the sum of polarization and charge-transfer components shows very little HB directional dependence. This new insight suggests that the difficulty for current nonpolarizable force fields to describe the HB directional dependence is not due to the lack of explicit polarization or charge-transfer terms. Using the DEDA results as reference, we further demonstrate that the main failure coming from the atomic point charge model can be overcome largely by introducing extra charge sites or higher order multipole moments. Among all the electrostatic models explored, the smeared charge distributed multipole model (up to quadrupole), which also takes account of charge penetration effects, gives the best agreement with the corresponding DEDA results. Meanwhile, our results indicate that the van der Waals interaction term needs to be further improved to better model directional HB.
AB - One well-known shortcoming of widely used biomolecular force fields is the description of the directional dependence of hydrogen bonding (HB). Here we aim to better understand the origin of this difficulty and thus provide some guidance for further force field development. Our theoretical approaches center on a novel density-based energy decomposition analysis (DEDA) method (J. Chem. Phys. 2009, 131, 164112), in which the frozen density energy is variationally determined through constrained search. This unique and most significant feature of DEDA enables us to find that the frozen density interaction term is the key factor in determining the HB orientation, while the sum of polarization and charge-transfer components shows very little HB directional dependence. This new insight suggests that the difficulty for current nonpolarizable force fields to describe the HB directional dependence is not due to the lack of explicit polarization or charge-transfer terms. Using the DEDA results as reference, we further demonstrate that the main failure coming from the atomic point charge model can be overcome largely by introducing extra charge sites or higher order multipole moments. Among all the electrostatic models explored, the smeared charge distributed multipole model (up to quadrupole), which also takes account of charge penetration effects, gives the best agreement with the corresponding DEDA results. Meanwhile, our results indicate that the van der Waals interaction term needs to be further improved to better model directional HB.
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U2 - 10.1021/ct2003226
DO - 10.1021/ct2003226
M3 - Article
AN - SCOPUS:83455218435
SN - 1549-9618
VL - 7
SP - 4038
EP - 4049
JO - Journal of chemical theory and computation
JF - Journal of chemical theory and computation
IS - 12
ER -