The role of structure and dynamics of an enzyme has been investigated at three different stages of its function including the chemical event it catalyzes. A one-pot computational method has been designed for each of these stages on the basis of classical and/or quantum mechanical-molecular mechanical molecular dynamics and transition path sampling simulations. For a pair of initial and final states A and B separated by a high free-energy barrier, using a two-stage selection process, several collective variables (CVs) are identified that can delineate A and B. However, these CVs are found to exhibit strong cross-coupling over the transition paths. A set of mutually orthogonal order parameters is then derived from these CVs and an optimal reaction coordinate, r, determined applying half-trajectory likelihood maximization along with a Bayesian information criterion. The transition paths are also used to project the multidimensional free energy surface and barrier crossing dynamics along r. The proposed scheme has been applied to the rate-determining intramolecular proton transfer reaction of the well-known enzyme human carbonic anhydrase II. The potential of mean force, F( r), in the absence of the chemical step is found to reproduce earlier results on the equilibrium population of two side-chain orientations of key residue His-64. Estimation of rate constants, k, from mean first passage times for the three different stages of catalysis shows that the rate-determining step of intramolecular proton transfer occurs with k ≃ 1.0 × 10 s, in close agreement with known experimental results.

We present, for the first time, how transient changes in the coordination number of zinc ion affects the rate determining step in the enzyme human carbonic anhydrase (HCA) II. The latter involves an intramolecular proton transfer between a zinc‐bound water and a distant histidine residue (His‐64). In the absence of time‐resolved experiments, results from classical and QM‐MM molecular dynamics and transition path sampling simulations are presented. The catalytic zinc ion is found to be present in two possible coordination states; viz. a stable tetra‐coordinated state, T and a less stable penta‐coordinated state, P with tetrahedral and trigonal bipyramidal coordination geometries, respectively. A fast dynamical inter‐conversion occurs between T and P due to reorganization of active site water molecules making the zinc ion more positively charged in state P. When initiated from different coordination environments, the most probable mechanism of proton transfer is found to be deprotonation of the equatorial water molecule from state P and transfer of the excess proton via a short path formed by hydrogen bonded network of active site water molecules. We estimate the rate constant of proton transfer as kP=1.29×106s-1 from P and kT=4.37×104s-1 from T. A quantitative match of estimated kP with the experimental value, (kexp∼0.8×106s-1 ) suggests that dynamics of Zn coordination triggers the rate determining proton transfer step in HCA II.

Dedicated to Professor Amit Basak on the occasion of his superannuationA series of novel non-planar phenothiazine-5-oxides (2a-l) bearing electron donating, electron withdrawing and bulky groups has been synthesized in high yields and their structural, photophysical, thermal and electronic properties are investigated and compared. All compounds are blue and blue-green emissive in solution (except 2g) and solid state respectively. Single crystal X-ray diffraction (XRD) studies of 2a, 2g, 2h, 2j and 2l indicated the effect of substituents on dihedral angles and non-planarity of the molecules; 2g and 2j with m-nitrophenyl/p-cyanophenyl as electron acceptor units exhibited "push-pull" behaviour with more planar structures, and D (donor) to A (acceptor) p-stacking interactions which was also evidenced by solvatochromic and DFT studies. Thermal gravimetric analysis (TGA) indicated good thermally stability of these compounds with thermal decomposition temperatures (T d ) in the range of 194-306 8C. Density functional theory (DFT) and time-dependent DFT approaches were employed to study the HOMO, LUMO and energy gap of these compounds.

A new technique for deposition of thin-film boron nitride (BN) from BN wafers has been demonstrated using a Q-switched ruby laser. The deposition rate was found to be∼7 Å/pulse at an energy density of 2.5 J cm−2. X-ray photoelectron spectroscopy was used to confirm the film composition. Infrared absorption peaks were observed at 802, 1370, and 1614 cm−1 characteristic of B—N bonds. The films were found to have an indirect band gap of 4.1 eV with resistivity in excess of 1011 Ω cm and breakdown fields between 3.0×105—1.0×106 V cm−1. The dielectric constant of the films was in the range 3.19–3.28. The minimum interface state density on InP as obtained from C-V (1 MHz) analysis was typically 6.2×1010 cm−2 eV−1, which increased to 4.1×1011 cm−2 eV−1 after annealing at 200 °C in argon. Scanning electron microscopy studies showed that this resulted in the development of micropores in the film.

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