Ab initio HF, MP2, CCSD(T) and hybrid density functional B3LYP calculations were performed on a series of skeletally mono- and di-substituted benzenes, (CH)₅Z and (CH)₄Z₂, Z = C^-, N, O⁺, Si^-, P, S⁺, Ge^-, As, Se⁺, BH^-, NH⁺, AlH^-, SiH, PH⁺, GaH^-, GeH and AsH⁺. Various measures of aromaticity such as the bond length equalization, homodesmic equations, singlet-triplet energy difference (AE_s-t), chemical hardness (η) and out-of-plane distortive tendency are critically analysed. The relative energy ordering in skeletally disubstituted benzenes displays trends that are inexplicable based on conventional wisdom. In general, the orthoisomer is found to be the least stable when the substituent is from the second row, whereas if the substituent is from the fourth row, the ortho-isomer is the most stable. Various qualitative arguments, including (a) lone pair-lone pair repulsion, (b) the sum of bond strengths in the twin Kekule forms, and (c) the rule of topological charge stabilization (TCS), are used to explain the observed relative energy trends. The rule of TCS in conjunction with the sum of bond strengths is found to predict the relative energy ordering reasonably well. The reactivity of this class of compounds is assessed based on their singlet-triplet energy differences, chemical hardness and the frequencies corresponding to out-of-plane skeletal distortions. These reactivity indices show less kinetic stability for the compounds with substituents from the fourth row and point to the fact that the thermodynamically most stable compounds need not be the least reactive ones. The ‡E_s-t values indicate that the π-framework of benzene weakens upon skeletal substitutions.

Bacillus halodurans (𝐵ℎ) ribonuclease H (RNase H) belongs to the nucleotidyl-transferase (NT) superfamily and is a prototypical member of a large family of enzymes that use two-metal ion (Mg²⁺ or Mn²⁺) catalysis to cleave nucleic acids. Long timescale molecular dynamics simulations have been performed on the 𝐵ℎRNase H-DNA-RNA hybrid complex and the respective monomers to understand the recognition mechanism, conformational preorganization, active site dynamics and energetics involved in the complex formation. Several structural and energetic analyses were performed and significant structural changes are observed in enzyme and hybrid duplex during complex formation. Hybrid molecule binding to RNase H enzyme leads to conformational changes in the DNA strand. The ability of the DNA strand in the hybrid duplex to sample conformations corresponding to typical A- and B-type nucleic acids and the characteristic minor groove width-seem to be crucial for efficient binding. Sugar moieties in certain positions interacting with the protein structure undergo notable conformational transitions. The water coordination and arrangement around the metal ions in active site region are quite stable, suggesting their important role in enzymatic catalysis. Details of key interactions found at the interface of enzyme-nucleic acid complex that are responsible for its stability are discussed.

3a is an accessory protein from SARS coronavirus that is known to play a significant role in the proliferation of the virus by forming tetrameric ion channels. Although the monomeric units are known to consist of three transmembrane (TM) domains, there are no solved structures available for the complete monomer. The present study proposes a structural model for the transmembrane region of the monomer by employing our previously tested approach, which predicts potential orientations of TM 𝛼-helices by minimizing the unfavorable contact surfaces between the different TM domains. The best model structure comprising all three 𝛼-helices has been subjected to MD simulations to examine its quality. The TM bundle was found to form a compact and stable structure with significant intermolecular interactions. The structural features of the proposed model of 3a account for observations from previous experimental investigations on the activity of the protein. Further analysis indicates that residues from the TM2 and TM3 domains are likely to line the pore of the ion channel, which is in good agreement with a recent experimental study. In the absence of an experimental structure for the protein, the proposed structure can serve as a useful model for inferring structure-function relationships about the protein.