Mixed implicit/explicit solvation models in quantum mechanical calculations of binding enthalpy for protein–ligand complexes

2006 ◽  
Vol 106 (8) ◽  
pp. 1943-1963 ◽  
Author(s):  
E. Nikitina ◽  
V. Sulimov ◽  
F. Grigoriev ◽  
O. Kondakova ◽  
S. Luschekina
Keyword(s):  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
Solvation Models ◽  
Binding Enthalpy ◽  
Explicit Solvation

scholarly journals Conformational Shifts of Stacked Heteroaromatics: Vacuum vs. Water Studied by Machine Learning

2021 ◽  
Vol 9 ◽  
Author(s):  
Johannes R. Loeffler ◽  
Monica L. Fernández-Quintero ◽  
Franz Waibl ◽  
Patrick K. Quoika ◽  
Florian Hofer ◽  
...  
Keyword(s):  
Drug Design ◽  
Quantum Mechanical ◽  
Stacking Interactions ◽  
Quantum Mechanical Calculations ◽  
Implicit Solvation ◽  
Small Molecule Drug ◽  
Dynamics Simulations ◽  
High Level ◽  
Explicit Solvation ◽  
Good Agreement

Stacking interactions play a crucial role in drug design, as we can find aromatic cores or scaffolds in almost any available small molecule drug. To predict optimal binding geometries and enhance stacking interactions, usually high-level quantum mechanical calculations are performed. These calculations have two major drawbacks: they are very time consuming, and solvation can only be considered using implicit solvation. Therefore, most calculations are performed in vacuum. However, recent studies have revealed a direct correlation between the desolvation penalty, vacuum stacking interactions and binding affinity, making predictions even more difficult. To overcome the drawbacks of quantum mechanical calculations, in this study we use neural networks to perform fast geometry optimizations and molecular dynamics simulations of heteroaromatics stacked with toluene in vacuum and in explicit solvation. We show that the resulting energies in vacuum are in good agreement with high-level quantum mechanical calculations. Furthermore, we show that using explicit solvation substantially influences the favored orientations of heteroaromatic rings thereby emphasizing the necessity to include solvation properties starting from the earliest phases of drug design.

Crystal Forms of Semisynthetic Ergot Alkaloid Terguride

2002 ◽  
Vol 67 (4) ◽  
pp. 479-489 ◽  
Author(s):  
Michal Hušák ◽  
Bohumil Kratochvíl ◽  
Ivana Císařová ◽  
Ladislav Cvak ◽  
Alexandr Jegorov ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Ergot Alkaloid ◽  
Simplified Model ◽  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
X Ray Diffraction ◽  
Torsion Angles ◽  
Crystal Forms ◽  
X Ray ◽  
Independent Molecules

Two new structures of semisynthetic ergot alkaloid terguride created by unusual number of symmetry-independent molecules were determined by X-ray diffraction methods at 150 K. Form A (monoclinic, P212121, Z = 12) contains three symmetry-independent terguride molecules and two molecules of water in the asymmetric part of the unit cell. The form CA (monoclinic, P21, Z = 8) is an anhydrate remarkable by the presence of four symmetry-independent molecules in the crystal structure. Conformations of twelve symmetry-independent molecules that were found in four already described terguride structures are compared with torsion angles obtained by ab initio quantum-mechanical calculations for the simplified model of N-cyclohexyl-N'-diethylurea.

Chemical accuracy from ‘Coulomb hole’ extrapolated molecular quantum-mechanical calculations

2001 ◽  
Vol 567-568 ◽  
pp. 375-384 ◽  
Author(s):  
K.L Bak ◽  
A Halkier ◽  
P Jørgensen ◽  
J Olsen ◽  
T Helgaker ◽  
...  
Keyword(s):  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
Coulomb Hole
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