Ligand interaction energies

In the next step, we focused on a possible correlation between the derived AutoDock scoring values and the YETI protein-ligand interaction energies and the observed biological data. In an attempt to correlate the scoring values and... 

Ab initio Calculations of Ion-Ligand Interaction Energies 2.1 Introduction... 

It is also known that geometry optimizations with too small basis sets may lead to non-realistic geometries especially if torsion angles or pyramidal structures are concerned 122>. In any case well-balanced basis sets are absolutely necessary, i.e. the quality of the basis set should be similar for all atoms. A carefully selected small GTO basis set may give reliable results for the ion-ligand interaction energies 31.125-i26> However, error compensations are at least partly responsible for this success. Therefore an improvement of the basis set may lead to less accurate results 91 >. Non-balanced small basis sets lead to large basis set superposition errors 126 l28>. This error is caused by the fact that in the calculations of the complex the wave functions... 

The importance of polarization functions (like d-orbitals for C, O and N or p-orbitals for H) for the calculation of ion-ligand interaction energies was pointed out by several authors 7J7 19>. Nevertheles many results using well-balanced small basis sets without polarization functions are acceptable if interactions of ligands with alkali or alkaline earth metal ions are considered (see Tables 1 and 3). The importance of the polarization functions in the case of the ammonium-water interaction was demonstrated recently 91>. 

G Naray-Szabo (1984) Quantum chemical calculation of the enzyme ligand interaction energy for trypsin inhibition by benzamidines, J Am Chem Soc 106( 16 ) 4584—4589... 

Isomer Isozyme N-C-C-N dihedral angle n Ar/Ar distance (A) Enzyme/ligand interaction energy (kcal/mol) Ligand internal energy (kcal/mol)... 

Antony J, Grimme S, Liakos DG, Neese E (2011) Protein-ligand interaction energies with dispersion corrected density functional theory and high-level wave function based methods. JPhys Chem A 115 11210-11220... 

Soderhjelm P, Aquilante F, Ryde U (2009) Calculation of protein-ligand interaction energies by a fragmentation approach combining high-level quantum chemistry with classical many-body effects. J Phys Chem B 113(32) 11085-11094... 

Note that S without a subscript is the direct correlation as defined in Chapter 3 on the other hand, S denotes a polymer with n ligands. Thus So is the empty polymer which is also denoted by P, Si the singly occupied polymer, etc.) In this particular model, the corresponding work is simply the direct ligand-ligand interaction energy U12. 

In the next step, the user selects one or more probes, such as CH3, CH3 (the default), H+, or H2O, that will be used to calculate probe-ligand interaction energies at each lattice point. All the energies associated with a particular probe-ligand pair constitute a molecular field. Probes are chosen to describe the enthalpic noncovalent forces important for binding. For example, the CHj, H+, and H2O probes describe the steric, electrostatic, and hydrogen bonding properties of molecules. 

The molecular field of a molecule is an ensemble of probe-ligand interaction energies. CoMFA treats each element of the field as an independent descriptor. If one computes steric and electrostatic fields over P grid points, the input table will contain 2 x P columns of explanatory variables. For N compounds, the matrix of molecular descriptors will consist of N x 2 X P cells. The table is three-dimensional because each column points to the coordinates at which its energy was calculated. By traversing the N cells along a single column, one can monitor the extent to which a probe, when placed at the associated point, is attracted or repelled by the various molecules. Each column describes localized differences in molecular fields. 

The Lennard-Jones steric energy between two atoms increases dramatically when the internuclear distance becomes shorter than the sum of the van der Waals radii. Consequently, two molecules, although their shapes are almost identical, may produce at a few lattice points enormously different interaction energies. To make such differences less influential in the final statistics, one usually truncates the probe—ligand interaction energies. The default in the CoMFA module of SYBYL is 30 kcal/mol, but others truncate the steric field at 4 or 5 kcal/mol.Klebe et al. reported the use of probe—ligand molecular similarity indices to overcome these problems. ... 

VALIDATE" " is a hybrid strategy where the ligand interaction energy (steric, electrostatic and induction) is computed via molecular mechanics. These energy terms were combined with a range of descriptors (rotatable bonds, calculated log P, steric fit, measures of complementary/uncomplementary contact between lipophilic/hydrophilic surfaces), and via partial... 

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