Short-Range Imbalances in the AMBER Lennard-Jones Potential for (Deoxy)Ribose center dot center dot center dot Nucleobase Lone-Pair center dot center dot center dot pi Contacts in Nucleic Acids

0555405 - BFÚ 2022 RIV US eng J - Článek v odborném periodiku
Mráziková, Klaudia - Šponer, Jiří - Mlýnský, Vojtech - Auffinger, P. - Kruse, Holger
Short-Range Imbalances in the AMBER Lennard-Jones Potential for (Deoxy)Ribose center dot center dot center dot Nucleobase Lone-Pair center dot center dot center dot pi Contacts in Nucleic Acids.
Journal of Chemical Information and Modeling. Roč. 61, č. 11 (2021), s. 5644-5657. ISSN 1549-9596. E-ISSN 1549-960X
Grant CEP: GA MŠMT EF15_003/0000477; GA ČR(CZ) GA21-23718S
Institucionální podpora: RVO:68081707
Klíčová slova: molecular-dynamics simulations * polarizable force-field * basis-sets * base stacking * b-dna
Obor OECD: Pharmacology and pharmacy
Impakt faktor: 6.162, rok: 2021
Způsob publikování: Open access
https://pubs.acs.org/doi/10.1021/acs.jcim.1c01047

The lone-pair center dot center dot center dot pi (lp center dot center dot center dot pi) (deoxy)ribose center dot center dot center dot nucleobase stacking is a recurring interaction in Z-DNA and RNAs that is characterized by subvan der Waals lp center dot center dot center dot pi contacts (<3.0 A). It is a part of the structural signature of CpG Z-step motifs in Z-DNA and r(UNCG) tetraloops that are known to behave poorly in molecular dynamics (MD) simulations. Although the exact origin of the MD simulation issues remains unclear, a significant part of the problem might be due to an imbalanced description of nonbonded interactions, including the characteristic lp center dot center dot center dot pi stacking. To gain insights into the links between lp center dot center dot center dot pi stacking and MD, we present an in-depth comparison between accurate large-basis-set double-hybrid Kohn-Sham density functional theory calculations DSD-BLYP-D3/ma-def2-QZVPP (DHDF-D3) and data obtained with the nonbonded potential of the AMBER force field (AFF) for NpN Z-steps (N = G, A, C, and U). Among other differences, we found that the AFF overestimates the DHDF-D3 lp center dot center dot center dot pi distances by similar to 0.1-0.2 A, while the deviation between the DHDF-D3 and AFF descriptions sharply increases in the short-range region of the interaction. Based on atom-in-molecule polarizabilities and symmetry-adapted perturbation theory analysis, we inferred that the DHDF-D3 versus AFF differences partly originate in identical nucleobase carbon atom Lennard-Jones (LJ) parameters despite the presence/absence of connected electron-withdrawing groups that lead to different effective volumes or vdW radii. Thus, to precisely model the very short CpG lp center dot center dot center dot pi contact distances, we recommend revision of the nucleobase atom LJ parameters. Additionally, we suggest that the large discrepancy between DHDF-D3 and AFF short-range repulsive part of the interaction energy potential may significantly contribute to the poor performances of MD simulations of nucleic acid systems containing Z-steps. Understanding where, and if possible why, the point-charge-type effective potentials reach their limits is vital for developing next-generation FFs and for addressing specific issues in contemporary MD simulations.
Trvalý link: http://hdl.handle.net/11104/0329926