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The interactions between the aromatic portion of the fluorinated n-(4-sulfamylbenzoyl)benzylamine (SBB) inhibitors and two residues of Human Carbonic Anhydrase II (HCAII)- Phe-131 and Pro-202 are studied. The structure of proteins is determined by the interactions between aromatic rings.

Potential energy curves are produced for the halogen bonding interactions of several halobenzene-formaldehyde complexes. The results have shown that for most halogen substituents, a halobenzene and formaldehyde form stable halogen bonded complexes with interaction energies that increase as the size of the halogen substituent increases.

A study was conducted to determine the relative magnitudes of the various interactions that occur between different steroid hormones and residues found within the binding pocket of mutated mineralocorticoid (MR). The results obtained revealed a strong hydrogen bond between progesterone and Thr945 and a relatively strong hydrophobic interaction between progesterone and Asn770.

The performance of the MP2 method, when paired with several different medium and extended basis sets, is assessed for the accurate computations of binding energies of hydrogen bonded and dispersion bound biologically derived complexes. It is shown that generally the MP2 technique, when paired with any basis set, does not yield reliable results for cyclic hydrogen bonds such as those seen in nucleic acid base pairs.

The effects of solvation on the stability of the hydrophobic core of the protein rubredoxin are evaluated. The results have indicated that short-range interactions between amino acid side chains are among the forces that contribute to the stability of rubredoxin and the solvation plays a pronounced role in the overall stability of the protein's hydrophobic core.

Potential energy curves for the interaction energies of a set of edge-to-face fluorine substituted benzene dimers is studied in an attempt to clarify the counterintuitive role of fluorination on the aromatic interactions found within the N-(4-sulfamylbenzoyl)benzylamine-Human Carbonic Anhydrase II (SBB-HCAII) complex. However, findings do not explain the crystallographic findings for the SBB-HCAII protein-ligand complex, where increased fluorination resulted in closer edge-to-face contacts, suggesting that there are factors, other than edge-to-face aromatic interactions, influencing the system's behavior.

The pairwise decomposition of the interaction energy between the protein human carbonic anhydrase II (HCA II) and the fluorine-substituted ligand N-(4-sulfamylbenzoyl)benzylamine (SBB) are calculated using semiempirical quantum mechanics based methods. The interaction between the ligand and the protein is dissected by dividing the ligand and the protein into subsystems to understand the structure-activity relationships as a result of fluorine substitution.

Here, we investigate the strengths of R-X···π interactions, involving both chlorine and bromine, in model systems derived from protein-ligand complexes found in the PDB. We find that the strengths of these interactions can vary significantly, with binding energies ranging from -2.01 to -3.60 kcal/mol. Symmetry adapted perturbation theory (SAPT) analysis shows that, as would be expected, dispersion plays the largest role in stabilizing these R-X···π interactions, generally accounting for about 50% to 80% of attraction. R-Br···π interactions are, for the most part, found to be stronger than R-Cl···π interactions, although the relative geometries of the interacting pair and the halogen's chemical environment can also have a strong impact. The two factors that have the strongest impact on the strength of these R-X···π interactions is the distance between the halogen and the phenyl plane as well as the size of the halogen σ-hole. [ABSTRACT FROM AUTHOR]

Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. This review provides a summary of known endogenous, naturally occurring, and synthetic ligands. The review also offers considerations from a molecular modeling perspective with which to design more specific LXRβ ligands based on the interaction energies of ligands and the important amino acid residues in the LXRβ ligand binding domain. [ABSTRACT FROM AUTHOR]